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Applied neurophysiology of the horse; implications for training, husbandry and welfare.Sebastian D. McBride1*, Matthew O. Parker2, Kirsty Roberts3, and Andrew Hemmings3. 1 Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Ceredigion,SY23 3FG, UK.2 School of Health Sciences and Social Work, James Watson West building, 2 King Richard 1st Road, Portsmouth, Hampshire, PO1 2FR 3 Royal Agricultural University, Cirencester, Gloucestershire, Gl7 6JS, UK.* Corresponding author: sdm@aber.ac.uk; tel. 01970 621633AbstractUnderstanding the neural circuits underlying equine behaviour has the potential to help optimise strategies of husbandry and training. This review discusses two areas of neurophysiological research in a range of species and relates this information to the horse. The first discussion focuses on mechanisms of learning and motivation and assesses how this information can be applied to improve the training of the horse. The second concerns the identification of the equine neurophysiological phenotype, through behavioural and genetic probes, as a way of improving strategies for optimal equine husbandry and training success. The review finishes by identifying directions for future research with an emphasis on how neurophysiological systems (and thus behaviour) can be modified through strategic husbandry. This review highlights how a neurophysioloigical understanding of horse behaviour can play an important future role to play in attaining the primary objectives of equitation science as well as improving the welfare of the horse. Keywords: horse, neurophysiology, behaviour, endophenotype, equitation science, welfare1.0 IntroductionMuch is known about the behaviour of horses as a result of an increasing body of applied research. This greatly improves our ability to keep and train the horse in optimal ways. Understanding the neural circuits underlying equine behaviour has the potential to further optimise these strategies of husbandry and training. The aim of this review is to present general and equine specific neurophysiological information within a translational framework, and by doing so, enhance the knowledge base of equitation science from a practical perspective. Two main areas of neurophysiological evidence will be discussed. The first relates to mechanisms of learning and motivation and thus the training of the horse. The second concerns the identification of the equine neurophysiological phenotype, through behavioural and genetic probes, as a way of improving strategies of equine husbandry and training. The review concludes with a discussion on areas of future research focusing on how neurophysiological systems can potentially be modulated, in a way that is both beneficial to horse (welfare) and rider (performance). In addition, the issue of performance versus welfare will be addressed throughout the review, focusing particularly on how added neurophysiological insight has the potential to help improve performance without diminishing welfare and vice versa. The review will start by outlining the key anatomical structures of the equine central nervous system that are relevant to behavioural output.2.0 Equine central nervous system relevant to behavioural outputIn order to behave appropriately in the context of shifting environmental constraints, the horse’s brain must gather information from sensory receptors such as the retinae and epithelial somatosensory receptors, and convey these via the sensory branches of the peripheral nervous system (PNS) to the spine and then the brain. Following a process of integration, influenced by a combination of genomic, genetic and epigenetic processes as well as prior experience (learning), an appropriate behavioural response is issued to effectors via the motor pathways of the PNS. This section will focus on the primary brain structures involved with the integration process, with a focus on the basal ganglia, a group of structures that have received most research attention in the horse, due to their pivotal role in the ordering of behavioural output. 2.1 Basal GangliaFigure 1 presents the primary structures of the basal ganglia. These include the striatum, the subthalamic nucleus (STN), globus pallidus (GP; internal: GPi; external: GPe), substantia nigra (SN; pars compacta: SNc; pars reticula: SNr) and ventral tegmental area (VTA). The striatum forms the main neural gateway to the basal ganglia and comprises the caudate, located dorsomedially (DMS), the putamen, located dorsolaterally (DLS), and the nucleus accumbens (NAc), located within the ventral aspect. The NAc can be further separated functionally and anatomically into the shell (NAcs) and core (NAcc) region. The striatum is made up of medium-spiny projection neurons (MSNs) and interneurons (cholinergic and GABAergic) ADDIN EN.CITE <EndNote><Cite><Author>Voorn</Author><Year>2004</Year><RecNum>4642</RecNum><IDText>Putting a spin on the dorsal-ventral divide of the striatum</IDText><DisplayText>(Voorn et al., 2004)</DisplayText><record><rec-number>4642</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820371">4642</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Voorn, P.</author><author>Vanderschuren, L. J.</author><author>Groenewegen, H. J.</author><author>Robbins, T. W.</author><author>Pennartz, C. M.</author></authors></contributors><auth-address>Department of Anatomy, Research Institute Neurosciences, VU University Medical Center, MF-G-102, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.</auth-address><titles><title>Putting a spin on the dorsal-ventral divide of the striatum</title><secondary-title>Trends Neurosci</secondary-title></titles><periodical><full-title>Trends in Neurosciences</full-title><abbr-1>Trends Neurosci</abbr-1><abbr-2>Trends Neurosci</abbr-2></periodical><pages>468-74</pages><volume>27</volume><number>8</number><edition>2004/07/24</edition><keywords><keyword>Animals</keyword><keyword>Basal Ganglia/anatomy & histology/physiology</keyword><keyword>Corpus Striatum/*anatomy & histology/*physiology</keyword><keyword>Humans</keyword><keyword>Nerve Net/anatomy & histology/physiology</keyword><keyword>Neural Pathways/*anatomy & histology/*physiology</keyword></keywords><dates><year>2004</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0166-2236 (Print)</isbn><accession-num>15271494</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>(Voorn et al., 2004) that receive input (afferents) from the cortex, hippocampus, thalamus, amygdala, dorsal raphe nucleus, STN and from different mid-brain structures (SNc and VTA) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWJlcjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (Haber, 2011; Wall et al., 2013). With regard to the cortex, there is a generalized but graded arrangement of cognitive control and reward areas (e.g. prefrontal cortex) sending projection neurons to the ventral striatum (NAc and ventral caudate), association areas (e.g. parietal cortex) innervating dorso-medial striatum and finally motor areas (e.g. motor cortex) innervating dorsolateral striatum PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWJlcjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (Haber, 2011; Choi et al., 2012) (Figure 1). Figure 1 about hereStriatal MSNs have a ‘many to one’ arrangement such that only specific combinations of dendritic activity, which originate from a range of cortical and sub-cortical structures, may elicit an MSN action potential PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaW5rPC9BdXRob3I+PFllYXI+MTk5NjwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (Mink, 1996; Wickens and Arbuthnott, 2010). Research to date suggests that cortical information is transferred via the basal ganglia to the thalamus and back to the cortex through three different pathways; the direct and indirect pathway through the striatum and the hyperdirect pathway through the STN PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXVyaWNlPC9BdXRob3I+PFllYXI+MTk5OTwvWWVhcj48
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ADDIN EN.CITE.DATA (Maurice et al., 1999; Gerfen and Bolam, 2010; Haynes and Haber, 2013).The direct pathway consists of a direct inhibitory GABAergic projection from the striatum to the SNr/GPi which also projects GABAergic neurons onto the thalamus. This double inhibitory system means that cortical input into the striatum has the potential to disinhibit the thalamus allowing a return of information back to the cortex ADDIN EN.CITE <EndNote><Cite><Author>Gerfen</Author><Year>2010</Year><RecNum>5461</RecNum><IDText>Chapter 1 - The Neuroanatomical Organization of the Basal Ganglia</IDText><DisplayText>(Gerfen and Bolam, 2010)</DisplayText><record><rec-number>5461</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820450">5461</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Gerfen, Charles R.</author><author>Bolam, J. Paul</author></authors><secondary-authors><author>Heinz Steiner and Kuei, Y. Tseng</author></secondary-authors></contributors><titles><title>Chapter 1 - The Neuroanatomical Organization of the Basal Ganglia</title><secondary-title>Handbook of Behavioral Neuroscience</secondary-title></titles><pages>3-28</pages><volume>Volume 20</volume><dates><year>2010</year></dates><publisher>Elsevier</publisher><isbn>1569-7339</isbn><urls><related-urls><url>;(Gerfen and Bolam, 2010) and an overall excitatory effect. Cells of the direct pathway are rich in dopamine receptors of the D1 family (comprising D1 and D5 sub-groups), which receive dopamine (dopamine) influx from the SNpc, (discussed in the following section PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Bb3Nha2k8L0F1dGhvcj48WWVhcj4xOTk4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (Aosaki et al., 1998; Stolzenberg et al., 2010). By contrast, the net effect of indirect pathway activity is that of cortical inhibition ADDIN EN.CITE <EndNote><Cite><Author>Presti</Author><Year>2005</Year><RecNum>1544</RecNum><IDText>Striatal opioid peptide content in an animal model of spontaneous stereotypic behavior</IDText><DisplayText>(Presti and Lewis, 2005)</DisplayText><record><rec-number>1544</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819935">1544</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Presti, M. F.</author><author>Lewis, M. H.</author></authors></contributors><titles><title>Striatal opioid peptide content in an animal model of spontaneous stereotypic behavior</title><secondary-title>Behavioural Brain Research</secondary-title><alt-title>Behav. Brain Res.</alt-title><short-title>Striatal opioid peptide content in an animal model of spontaneous stereotypic behavior</short-title></titles><periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></periodical><alt-periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></alt-periodical><pages>363-368</pages><volume>157</volume><number>2 <Go to ISI>://000226702500018</number><dates><year>2005</year><pub-dates><date>Feb 28</date></pub-dates></dates><accession-num>ISI:000226702500018</accession-num><urls></urls></record></Cite></EndNote>(Presti and Lewis, 2005). This is achieved through inhibitory GABAergic projections from the striatum to the GPe which then projects inhibitory GABAergic neurons onto both the SNr/GPi and STN. The inhibitory neurons onto SNr/GPi form a triple inhibition system such that cortical initiation of the indirect pathway results in increased inhibition of the thalamic output and thus attenuated return of cortical information. MSN’s of the indirect pathway express dopamine receptors of the D2 family (comprising D2, D3 and D4 subtypes), which are negatively coupled to adenyl cyclase stimulation ADDIN EN.CITE <EndNote><Cite><Author>McPherson</Author><Year>2000</Year><RecNum>5981</RecNum><IDText>Substantia nigra glutamate antagonists produce contralateral turning and basal ganglia Fos expression: Interactions with D1 and D2 dopamine receptor agonists</IDText><DisplayText>(McPherson and Marshall, 2000)</DisplayText><record><rec-number>5981</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820485">5981</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McPherson, R. J.</author><author>Marshall, J. F.</author></authors></contributors><titles><title>Substantia nigra glutamate antagonists produce contralateral turning and basal ganglia Fos expression: Interactions with D1 and D2 dopamine receptor agonists</title><secondary-title>Synapse</secondary-title></titles><periodical><full-title>Synapse</full-title><abbr-1>Synapse</abbr-1><abbr-2>Synapse</abbr-2></periodical><pages>194-204</pages><volume>36</volume><number>3</number><dates><year>2000</year><pub-dates><date>Jun 1</date></pub-dates></dates><isbn>0887-4476</isbn><accession-num>WOS:000086798200004</accession-num><urls><related-urls><url><Go to ISI>://WOS:000086798200004</url></related-urls></urls><electronic-resource-num>10.1002/(sici)1098-2396(20000601)36:3<194::aid-syn4>3.0.co;2-d</electronic-resource-num></record></Cite></EndNote>(McPherson and Marshall, 2000). Activation of D2 populations by SNpc dopamine projections, effectively dampens the inhibitory drive associated with indirect MSN activity ADDIN EN.CITE <EndNote><Cite><Author>Nicola</Author><Year>2000</Year><RecNum>1340</RecNum><IDText>Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens</IDText><DisplayText>(Nicola et al., 2000)</DisplayText><record><rec-number>1340</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819919">1340</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nicola, S. M.</author><author>Surmeier, D. T.</author><author>Malenka, R. C.</author></authors></contributors><titles><title>Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens</title><secondary-title>Annual Review Of Neuroscience</secondary-title><short-title>Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens</short-title></titles><periodical><full-title>Annual Review of Neuroscience</full-title><abbr-1>Annu. Rev. Neurosci.</abbr-1><abbr-2>Annu Rev Neurosci</abbr-2></periodical><pages>185-215</pages><volume>23</volume><dates><year>2000</year></dates><accession-num>ISI:000086730500007</accession-num><urls><related-urls><url><Go to ISI>://000086730500007</url></related-urls></urls></record></Cite></EndNote>(Nicola et al., 2000), thereby disinhibiting the thalamo-cortical motor projection (discussed further in the following section) . 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ADDIN EN.CITE.DATA (Haynes et al., 2004). Primary STN efferents are glutamatergic and thus excitatory, targeting both pallidal structures of the direct and indirect pathway (SNr/Gpi and GPe respectively) ADDIN EN.CITE <EndNote><Cite><Author>Charpier</Author><Year>2010</Year><RecNum>5475</RecNum><IDText>Chapter 15 - The Subthalamic Nucleus: From In Vitro to In Vivo Mechanisms</IDText><DisplayText>(Charpier et al., 2010)</DisplayText><record><rec-number>5475</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820451">5475</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Charpier, Stephane</author><author>Beurrier, Corinne</author><author>Paz, Jeanne T.</author></authors><secondary-authors><author>Heinz Steiner and Kuei, Y. Tseng</author></secondary-authors></contributors><titles><title>Chapter 15 - The Subthalamic Nucleus: From In Vitro to In Vivo Mechanisms</title><secondary-title>Handbook of Behavioral Neuroscience</secondary-title></titles><pages>259-273</pages><volume>Volume 20</volume><dates><year>2010</year></dates><publisher>Elsevier</publisher><isbn>1569-7339</isbn><urls><related-urls><url>;(Charpier et al., 2010). Theoretically the STN has the opportunity to increase activation of the both the direct and indirect pathway but it is also modulated by the GABAergic feedback loop from GPe back to STN ADDIN EN.CITE <EndNote><Cite><Author>Charpier</Author><Year>2010</Year><RecNum>5475</RecNum><IDText>Chapter 15 - The Subthalamic Nucleus: From In Vitro to In Vivo Mechanisms</IDText><DisplayText>(Charpier et al., 2010)</DisplayText><record><rec-number>5475</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820451">5475</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Charpier, Stephane</author><author>Beurrier, Corinne</author><author>Paz, Jeanne T.</author></authors><secondary-authors><author>Heinz Steiner and Kuei, Y. Tseng</author></secondary-authors></contributors><titles><title>Chapter 15 - The Subthalamic Nucleus: From In Vitro to In Vivo Mechanisms</title><secondary-title>Handbook of Behavioral Neuroscience</secondary-title></titles><pages>259-273</pages><volume>Volume 20</volume><dates><year>2010</year></dates><publisher>Elsevier</publisher><isbn>1569-7339</isbn><urls><related-urls><url>;(Charpier et al., 2010). This complex relationship of the STN in modulating and being modulated by other basal ganglia structures results in a signature triphasic response of the SNr (the primary output structure to the thalamus); firstly it shows early excitation as a result of hyperdirect pathway activation via the STN, this is followed by inhibition as a result of the GABAergic direct pathway activation, and finally it shows late excitation as a result of the activation of the indirect pathway PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OYWthbmlzaGk8L0F1dGhvcj48WWVhcj4xOTg4PC9ZZWFy
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ADDIN EN.CITE.DATA (Gerdeman et al., 2003; Di Filippo et al., 2009). The effect of dopamine transmitter release on the striatum, however, is dependent on the type of MSN within the striatum. For MSNs that express DRD1, muscarinic M4 receptors, dynorphin (κ-opioid receptor) and substance P, dopamine has an excitatory effect, stimulating the direct pathway ADDIN EN.CITE <EndNote><Cite><Author>Kreitzer</Author><Year>2009</Year><RecNum>2430</RecNum><IDText>Physiology and Pharmacology of Striatal Neurons</IDText><DisplayText>(Kreitzer, 2009)</DisplayText><record><rec-number>2430</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820116">2430</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kreitzer, A. C.</author></authors></contributors><titles><title>Physiology and Pharmacology of Striatal Neurons</title><secondary-title>Annual Review of Neuroscience</secondary-title></titles><periodical><full-title>Annual Review of Neuroscience</full-title><abbr-1>Annu. Rev. Neurosci.</abbr-1><abbr-2>Annu Rev Neurosci</abbr-2></periodical><pages>127-147</pages><volume>32</volume><dates><year>2009</year></dates><isbn>0147-006X</isbn><accession-num>WOS:000268504100006</accession-num><urls><related-urls><url><Go to ISI>://WOS:000268504100006</url></related-urls></urls><electronic-resource-num>10.1146/annurev.neuro.051508.135422</electronic-resource-num></record></Cite></EndNote>(Kreitzer, 2009). For MSNs that contain DRD2 and adenosine A2a receptors, and express enkephalin (delta opioid receptor), dopamine has an inhibitory effect, stimulating the indirect pathway ADDIN EN.CITE <EndNote><Cite><Author>Kreitzer</Author><Year>2009</Year><RecNum>2430</RecNum><IDText>Physiology and Pharmacology of Striatal Neurons</IDText><DisplayText>(Kreitzer, 2009)</DisplayText><record><rec-number>2430</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820116">2430</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kreitzer, A. C.</author></authors></contributors><titles><title>Physiology and Pharmacology of Striatal Neurons</title><secondary-title>Annual Review of Neuroscience</secondary-title></titles><periodical><full-title>Annual Review of Neuroscience</full-title><abbr-1>Annu. Rev. Neurosci.</abbr-1><abbr-2>Annu Rev Neurosci</abbr-2></periodical><pages>127-147</pages><volume>32</volume><dates><year>2009</year></dates><isbn>0147-006X</isbn><accession-num>WOS:000268504100006</accession-num><urls><related-urls><url><Go to ISI>://WOS:000268504100006</url></related-urls></urls><electronic-resource-num>10.1146/annurev.neuro.051508.135422</electronic-resource-num></record></Cite></EndNote>(Kreitzer, 2009). Dopamine neurons from the SNc (nigrostriatal pathway) and VTA (mesoaccumbens pathway) directly target different striatal structures with the SNc modulating MSNs within the dorsal striatum (caudate and putamen) whereas the VTA modulates the ventral striatum (nucleus accumbens) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYWxpdmFzPC9BdXRob3I+PFllYXI+MTk4MzwvWWVhcj48
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ADDIN EN.CITE.DATA (Kalivas et al., 1983). Neurons along the nigrostrital and mesoaccumbens that fire continuously at a low firing rate and are referred to as 'tonic' whereas sudden increases in firing rate as a result of environmental effects are referred to as 'phasic' dopamine release ADDIN EN.CITE <EndNote><Cite><Author>Surmeier</Author><Year>2007</Year><RecNum>2400</RecNum><IDText>D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons</IDText><DisplayText>(Surmeier et al., 2007)</DisplayText><record><rec-number>2400</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820113">2400</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Surmeier, D. J.</author><author>Ding, J.</author><author>Day, M.</author><author>Wang, Z. F.</author><author>Shen, W. X.</author></authors></contributors><titles><title>D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons</title><secondary-title>Trends in Neurosciences</secondary-title></titles><periodical><full-title>Trends in Neurosciences</full-title><abbr-1>Trends Neurosci.</abbr-1><abbr-2>Trends Neurosci</abbr-2></periodical><pages>228-235</pages><volume>30</volume><number>5</number><dates><year>2007</year></dates><isbn>0166-2236</isbn><accession-num>WOS:000246752000007</accession-num><urls><related-urls><url><Go to ISI>://WOS:000246752000007</url></related-urls></urls><electronic-resource-num>10.1016/j.tins.2007.03.008</electronic-resource-num></record></Cite></EndNote>(Surmeier et al., 2007).2.3. Reciprocal and non-reciprocal loops from the striatum to mid-brain structures A major feature of striatal to mid-brain connectivity is the mechanism of reciprocal feedback combined with non-reciprocal feed-forward. This allows regions of the striatum to modulate their own dopamine afferents (reciprocal feedback) but also to affect mid-brain dopamine modulation of other regions of the striatum (non-reciprocal feed-forward) ADDIN EN.CITE <EndNote><Cite><Author>Haber</Author><Year>2000</Year><RecNum>5998</RecNum><IDText>Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum</IDText><DisplayText>(Haber et al., 2000)</DisplayText><record><rec-number>5998</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5998</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Haber, S. N.</author><author>Fudge, J. L.</author><author>McFarland, N. R.</author></authors></contributors><titles><title>Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum</title><secondary-title>Journal of Neuroscience</secondary-title><alt-title>J. Neurosci.</alt-title><short-title>Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum</short-title></titles><periodical><full-title>Journal of Neuroscience</full-title><abbr-1>J. Neurosci.</abbr-1><abbr-2>J Neurosci</abbr-2></periodical><alt-periodical><full-title>Journal of Neuroscience</full-title><abbr-1>J. Neurosci.</abbr-1><abbr-2>J Neurosci</abbr-2></alt-periodical><pages>2369-2382</pages><volume>20</volume><number>6 <Go to ISI>://000085724200035</number><dates><year>2000</year><pub-dates><date>Mar 15</date></pub-dates></dates><accession-num>ISI:000085724200035</accession-num><urls></urls></record></Cite></EndNote>(Haber et al., 2000). This arrangement is such that dopamine innervation of the NAc, as well as resulting in feedback to this same region, also has a feed-forward effect on the caudate (DMS) portion of the striatum. What is critical to the mechanism is that feedback is through a direct mechanism, which causes inhibition, but feed-forward is via indirect GABA inter-neurons which has an overall excitatory effect. In a similar fashion, DMS negatively feedbacks on itself but positively feeds to the DLS ADDIN EN.CITE <EndNote><Cite><Author>Haber</Author><Year>2000</Year><RecNum>5998</RecNum><IDText>Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum</IDText><DisplayText>(Haber et al., 2000)</DisplayText><record><rec-number>5998</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5998</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Haber, S. N.</author><author>Fudge, J. L.</author><author>McFarland, N. R.</author></authors></contributors><titles><title>Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum</title><secondary-title>Journal of Neuroscience</secondary-title><alt-title>J. Neurosci.</alt-title><short-title>Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum</short-title></titles><periodical><full-title>Journal of Neuroscience</full-title><abbr-1>J. Neurosci.</abbr-1><abbr-2>J Neurosci</abbr-2></periodical><alt-periodical><full-title>Journal of Neuroscience</full-title><abbr-1>J. Neurosci.</abbr-1><abbr-2>J Neurosci</abbr-2></alt-periodical><pages>2369-2382</pages><volume>20</volume><number>6 <Go to ISI>://000085724200035</number><dates><year>2000</year><pub-dates><date>Mar 15</date></pub-dates></dates><accession-num>ISI:000085724200035</accession-num><urls></urls></record></Cite></EndNote>(Haber et al., 2000). 3.0 Learning and motivationOperant learning theory is partitioned into positive reinforcement, negative reinforcement and punishment. Reinforcement is the strengthening of a behavioural response to a discriminative stimulus [cue] either through the introduction of an appetitive stimulus [positive reinforcement] or the removal of an aversive stimulus [negative reinforcement] as a consequence of the animal's response. 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ADDIN EN.CITE.DATA (Warren-Smith and McGreevy, 2007; Warren-Smith and McGreevy, 2008; Hockenhull and Creighton, 2010). Within reinforcement learning there are also three sequential phases of the learning process, acquisition, action-outcome and habit formation ADDIN EN.CITE <EndNote><Cite><Author>Dickinson</Author><Year>1985</Year><RecNum>5997</RecNum><IDText>Actions and habits- the development of behavioural autonomy.</IDText><DisplayText>(Dickinson, 1985)</DisplayText><record><rec-number>5997</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5997</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dickinson, A.</author></authors></contributors><titles><title>Actions and habits- the development of behavioural autonomy.</title><secondary-title>Philosophical Transactions of the Royal Society of London Series B-Biological Sciences</secondary-title></titles><pages>67-78</pages><volume>308</volume><number>1135</number><dates><year>1985</year><pub-dates><date>1985</date></pub-dates></dates><isbn>0962-8436</isbn><accession-num>WOS:A1985ACG3700005</accession-num><urls><related-urls><url><Go to WoS>://WOS:A1985ACG3700005</url></related-urls></urls><electronic-resource-num>10.1098/rstb.1985.0010</electronic-resource-num></record></Cite></EndNote>(Dickinson, 1985). For the purposes of understanding how the basal ganglia orchestrates these learning processes, the mechanisms underpinning learning through positive reinforcement will be discussed first, and then extended to describe the three aforementioned phases of the generalized learning process. This will provide a basis for discussion of the mechanisms underpinning both negative reinforcement and punishment. 3.1 Neural mechanisms underpinning positive reinforcementThrough a process of associative learning, objects, environments and events become predictive of the arrival of other biologically relevant stimuli where the attainment (positive) or removal (negative) of those stimuli are linked to specific behavioural sequences (operant response) ADDIN EN.CITE <EndNote><Cite><Author>Yin</Author><Year>2008</Year><RecNum>2396</RecNum><IDText>Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks</IDText><DisplayText>(Yin et al., 2008)</DisplayText><record><rec-number>2396</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820113">2396</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yin, H. H.</author><author>Ostlund, S. B.</author><author>Balleine, B. W.</author></authors></contributors><titles><title>Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks</title><secondary-title>European Journal of Neuroscience</secondary-title></titles><periodical><full-title>European Journal of Neuroscience</full-title><abbr-1>Eur. J. Neurosci.</abbr-1><abbr-2>Eur J Neurosci</abbr-2></periodical><pages>1437-1448</pages><volume>28</volume><number>8</number><dates><year>2008</year></dates><isbn>0953-816X</isbn><accession-num>WOS:000260050500001</accession-num><urls><related-urls><url><Go to ISI>://WOS:000260050500001</url></related-urls></urls><electronic-resource-num>10.1111/j.1460-9568.2008.06422.x</electronic-resource-num></record></Cite></EndNote>(Yin et al., 2008). An operant response to attain a reward is referred to as positive reinforcement whereas an operant response in order to remove a negative stimulus (escape) or to avoid the arrival of a negative stimulus (avoidance) is referred to as negative reinforcement. Once learnt, subsequent presentation of cues grab attention and elicits motivation towards appetitive/evasive behaviours to re-attain the same goal ADDIN EN.CITE <EndNote><Cite><Author>Mackintosh</Author><Year>1975</Year><RecNum>5999</RecNum><IDText>Theory of attention- variations in associability of stimuli with reinforcement</IDText><DisplayText>(Mackintosh, 1975)</DisplayText><record><rec-number>5999</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5999</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mackintosh, N. J.</author></authors></contributors><titles><title>Theory of attention- variations in associability of stimuli with reinforcement</title><secondary-title>Psychological Review</secondary-title></titles><periodical><full-title>Psychological Review</full-title><abbr-1>Psychol. Rev.</abbr-1><abbr-2>Psychol Rev</abbr-2></periodical><pages>276-298</pages><volume>82</volume><number>4</number><dates><year>1975</year><pub-dates><date>1975</date></pub-dates></dates><isbn>0033-295X</isbn><accession-num>WOS:A1975AJ15200003</accession-num><urls><related-urls><url><Go to WoS>://WOS:A1975AJ15200003</url></related-urls></urls><electronic-resource-num>10.1037/h0076778</electronic-resource-num></record></Cite></EndNote>(Mackintosh, 1975). Fundamental to these learning processes are the biological phenomena of long-term potentiation (LTP) and long-term depression (LTD) that strengthen or weaken the link between sensory input and motor output. 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ADDIN EN.CITE.DATA (Surmeier et al., 2007; Shen et al., 2008). The latter describes the process of extinction when the lack of reward presentation eventually produces no response from the animal. What is important to note is that changes in dopamine release are determined by the difference between what the animal expects as a reward and what is actually delivered. This differential value is referred to as the ‘reward prediction error’ ADDIN EN.CITE <EndNote><Cite><Author>Schultz</Author><Year>1997</Year><RecNum>1226</RecNum><IDText>A neural substrate of prediction and reward</IDText><DisplayText>(Schultz et al., 1997)</DisplayText><record><rec-number>1226</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819911">1226</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Schultz, W.</author><author>Dayan, P.</author><author>Montague, P. R.</author></authors></contributors><titles><title>A neural substrate of prediction and reward</title><secondary-title>Science</secondary-title><alt-title>Science</alt-title><short-title>A neural substrate of prediction and reward</short-title></titles><periodical><full-title>Science</full-title><abbr-1>Science</abbr-1><abbr-2>Science</abbr-2></periodical><alt-periodical><full-title>Science</full-title><abbr-1>Science</abbr-1><abbr-2>Science</abbr-2></alt-periodical><pages>1593-1599</pages><volume>275</volume><number>5306 <Go to ISI>://A1997WN12300029</number><dates><year>1997</year><pub-dates><date>Mar 14</date></pub-dates></dates><accession-num>ISI:A1997WN12300029</accession-num><urls></urls></record></Cite></EndNote>(Schultz et al., 1997). The dopamine response is greatest the first time the reward is presented (because it is completely unexpected), but then wanes with multiple presentations and is only re-kindled when an element of increased value or temporal unpredictability is re-inserted ADDIN EN.CITE <EndNote><Cite><Author>Bayer</Author><Year>2005</Year><RecNum>5827</RecNum><DisplayText>(Bayer and Glimcher, 2005)</DisplayText><record><rec-number>5827</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820475">5827</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bayer, H. M.</author><author>Glimcher, P. W.</author></authors></contributors><titles><title>Midbrain dopamine neurons encode a quantitative reward prediction error signal</title><secondary-title>Neuron</secondary-title></titles><periodical><full-title>Neuron</full-title><abbr-1>Neuron</abbr-1><abbr-2>Neuron</abbr-2></periodical><pages>129-141</pages><volume>47</volume><number>1</number><dates><year>2005</year><pub-dates><date>Jul 7</date></pub-dates></dates><isbn>0896-6273</isbn><accession-num>WOS:000230464000013</accession-num><urls><related-urls><url><Go to ISI>://WOS:000230464000013</url></related-urls></urls><electronic-resource-num>10.1016/j.neuron.2005.05.020</electronic-resource-num></record></Cite></EndNote>(Bayer and Glimcher, 2005). Conversely, if reward is expected but not presented, then this results in a reduction in tonic dopamine release. For example, in water deprived primates, bursts of activity in the dopaminergic VTA neurons were observed when unexpected juice was dispensed, whereas suppressions in tonic firing rate were recorded when expected rewards were withheld ADDIN EN.CITE <EndNote><Cite><Author>Mirenowicz</Author><Year>1994</Year><RecNum>958</RecNum><DisplayText>(Mirenowicz and Schultz, 1994; Schultz, 2002)</DisplayText><record><rec-number>958</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819889">958</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mirenowicz, J.</author><author>Schultz, W.</author></authors></contributors><titles><title>Importance of unpredictability for reward responses in primate dopamine neurons</title><secondary-title>Journal Of Neurophysiology</secondary-title><short-title>Importance of unpredictability for reward responses in primate dopamine neurons</short-title></titles><periodical><full-title>Journal of Neurophysiology</full-title><abbr-1>J. Neurophysiol.</abbr-1><abbr-2>J Neurophysiol</abbr-2></periodical><pages>1024-1027</pages><volume>72</volume><dates><year>1994</year></dates><label>564</label><urls></urls></record></Cite><Cite><Author>Schultz</Author><Year>2002</Year><RecNum>1437</RecNum><record><rec-number>1437</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819926">1437</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Schultz, W.</author></authors></contributors><titles><title>Getting formal with dopamine and reward</title><secondary-title>Neuron</secondary-title><alt-title>Neuron</alt-title><short-title>Getting formal with dopamine and reward</short-title></titles><periodical><full-title>Neuron</full-title><abbr-1>Neuron</abbr-1><abbr-2>Neuron</abbr-2></periodical><alt-periodical><full-title>Neuron</full-title><abbr-1>Neuron</abbr-1><abbr-2>Neuron</abbr-2></alt-periodical><pages>241-263</pages><volume>36</volume><number>2 <Go to ISI>://000178554700006</number><dates><year>2002</year><pub-dates><date>Oct 10</date></pub-dates></dates><accession-num>ISI:000178554700006</accession-num><urls></urls></record></Cite></EndNote>(Mirenowicz and Schultz, 1994; Schultz, 2002). 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ADDIN EN.CITE.DATA (Samejima et al., 2005; Morris et al., 2006). In this sense, the CS dopamine signal appears to have a gating function for specific cortical glutamatergic signals arriving at the striatum ADDIN EN.CITE <EndNote><Cite><Author>Frank</Author><Year>2001</Year><RecNum>2428</RecNum><IDText>Interactions between frontal cortex and basal ganglia in working memory: A computational model</IDText><DisplayText>(Frank et al., 2001)</DisplayText><record><rec-number>2428</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820116">2428</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Frank, Michael J.</author><author>Loughry, Bryan</author><author>O'Reilly, Randall C.</author></authors></contributors><titles><title>Interactions between frontal cortex and basal ganglia in working memory: A computational model</title><secondary-title>Cognitive Affective and Behavioral Neuroscience</secondary-title></titles><pages>137-160</pages><volume>1</volume><number>2</number><dates><year>2001</year></dates><isbn>1530-7026</isbn><accession-num>BIOSIS:PREV200200362591</accession-num><urls><related-urls><url><Go to ISI>://BIOSIS:PREV200200362591</url></related-urls></urls></record></Cite></EndNote>(Frank et al., 2001) that, through an system of competition, provide an neural architecture for an action selection process ADDIN EN.CITE <EndNote><Cite><Author>Prescott</Author><Year>2006</Year><RecNum>1589</RecNum><DisplayText>(Prescott et al., 2006)</DisplayText><record><rec-number>1589</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819939">1589</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Prescott, T. J.</author><author>Gonzalez, F. M. M.</author><author>Gurney, K.</author><author>Humphries, M. D.</author><author>Redgrave, P.</author></authors></contributors><titles><title>A robot model of the basal ganglia: Behavior and intrinsic processing</title><secondary-title>Neural Networks</secondary-title><short-title>A robot model of the basal ganglia: Behavior and intrinsic processing</short-title></titles><periodical><full-title>Neural Networks</full-title><abbr-1>Neural Networks</abbr-1><abbr-2>Neural Networks</abbr-2></periodical><pages>31-61</pages><volume>19</volume><number>1</number><dates><year>2006</year><pub-dates><date>Jan</date></pub-dates></dates><accession-num>ISI:000235261500002</accession-num><urls><related-urls><url><Go to ISI>://000235261500002</url></related-urls></urls></record></Cite></EndNote>(Prescott et al., 2006). The CS dopamine signal post-acquistion also arrives at the ventral striatum via the mesoaccumbens (VTA-NAc) dopamine pathway ADDIN EN.CITE <EndNote><Cite><Author>Schultz</Author><Year>1997</Year><RecNum>1225</RecNum><IDText>Dopamine neurons and their role in reward mechanisms</IDText><DisplayText>(Schultz, 1997)</DisplayText><record><rec-number>1225</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819911">1225</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Schultz, W.</author></authors></contributors><titles><title>Dopamine neurons and their role in reward mechanisms</title><secondary-title>Current Opinion in Neurobiology</secondary-title><alt-title>Curr. Opin. Neurobiol.</alt-title><short-title>Dopamine neurons and their role in reward mechanisms</short-title></titles><periodical><full-title>Current Opinion in Neurobiology</full-title><abbr-1>Curr. Opin. Neurobiol.</abbr-1><abbr-2>Curr Opin Neurobiol</abbr-2></periodical><alt-periodical><full-title>Current Opinion in Neurobiology</full-title><abbr-1>Curr. Opin. Neurobiol.</abbr-1><abbr-2>Curr Opin Neurobiol</abbr-2></alt-periodical><pages>191-197</pages><volume>7</volume><number>2 <Go to ISI>://A1997WZ21500007</number><dates><year>1997</year><pub-dates><date>Apr</date></pub-dates></dates><accession-num>ISI:A1997WZ21500007</accession-num><urls></urls></record></Cite></EndNote>(Schultz, 1997). Yin et al. ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1"><Author>Yin</Author><Year>2008</Year><RecNum>2396</RecNum><DisplayText>(2008)</DisplayText><record><rec-number>2396</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820113">2396</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yin, H. H.</author><author>Ostlund, S. B.</author><author>Balleine, B. W.</author></authors></contributors><titles><title>Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks</title><secondary-title>European Journal of Neuroscience</secondary-title></titles><periodical><full-title>European Journal of Neuroscience</full-title><abbr-1>Eur. J. Neurosci.</abbr-1><abbr-2>Eur J Neurosci</abbr-2></periodical><pages>1437-1448</pages><volume>28</volume><number>8</number><dates><year>2008</year></dates><isbn>0953-816X</isbn><accession-num>WOS:000260050500001</accession-num><urls><related-urls><url><Go to ISI>://WOS:000260050500001</url></related-urls></urls><electronic-resource-num>10.1111/j.1460-9568.2008.06422.x</electronic-resource-num></record></Cite></EndNote>(2008) postulated that phasic dopamine activation of MSNs in the NAc acts as an amplifier of actions that have already been selected. This would determine the vigour by the which the behaviour is performed, often referred to as motivation ADDIN EN.CITE <EndNote><Cite><Author>Yin</Author><Year>2008</Year><RecNum>2396</RecNum><IDText>Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks</IDText><DisplayText>(Yin et al., 2008)</DisplayText><record><rec-number>2396</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820113">2396</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yin, H. H.</author><author>Ostlund, S. B.</author><author>Balleine, B. W.</author></authors></contributors><titles><title>Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks</title><secondary-title>European Journal of Neuroscience</secondary-title></titles><periodical><full-title>European Journal of Neuroscience</full-title><abbr-1>Eur. J. Neurosci.</abbr-1><abbr-2>Eur J Neurosci</abbr-2></periodical><pages>1437-1448</pages><volume>28</volume><number>8</number><dates><year>2008</year></dates><isbn>0953-816X</isbn><accession-num>WOS:000260050500001</accession-num><urls><related-urls><url><Go to ISI>://WOS:000260050500001</url></related-urls></urls><electronic-resource-num>10.1111/j.1460-9568.2008.06422.x</electronic-resource-num></record></Cite></EndNote>(Yin et al., 2008), and is the considered mechanism whereby motivational properties are conferred to conditioned stimuli ADDIN EN.CITE <EndNote><Cite><Author>Yin</Author><Year>2008</Year><RecNum>2396</RecNum><IDText>Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks</IDText><DisplayText>(Yin et al., 2008)</DisplayText><record><rec-number>2396</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820113">2396</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yin, H. H.</author><author>Ostlund, S. B.</author><author>Balleine, B. W.</author></authors></contributors><titles><title>Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks</title><secondary-title>European Journal of Neuroscience</secondary-title></titles><periodical><full-title>European Journal of Neuroscience</full-title><abbr-1>Eur. J. Neurosci.</abbr-1><abbr-2>Eur J Neurosci</abbr-2></periodical><pages>1437-1448</pages><volume>28</volume><number>8</number><dates><year>2008</year></dates><isbn>0953-816X</isbn><accession-num>WOS:000260050500001</accession-num><urls><related-urls><url><Go to ISI>://WOS:000260050500001</url></related-urls></urls><electronic-resource-num>10.1111/j.1460-9568.2008.06422.x</electronic-resource-num></record></Cite></EndNote>(Yin et al., 2008). The strength of this signal is determined by the valence (positive or negative) of the unconditioned stimulus to which the CS is linked. Anatomically, it is the previously described non-reciprocal feed-forward connections via the mid-brain that allow the ventral striatum to modulate the gating processes of the dorsal striatum and thereby have this amplifying effect ADDIN EN.CITE <EndNote><Cite><Author>Haber</Author><Year>2000</Year><RecNum>5998</RecNum><IDText>Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum</IDText><DisplayText>(Haber et al., 2000)</DisplayText><record><rec-number>5998</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5998</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Haber, S. N.</author><author>Fudge, J. L.</author><author>McFarland, N. R.</author></authors></contributors><titles><title>Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum</title><secondary-title>Journal of Neuroscience</secondary-title><alt-title>J. Neurosci.</alt-title><short-title>Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum</short-title></titles><periodical><full-title>Journal of Neuroscience</full-title><abbr-1>J. Neurosci.</abbr-1><abbr-2>J Neurosci</abbr-2></periodical><alt-periodical><full-title>Journal of Neuroscience</full-title><abbr-1>J. Neurosci.</abbr-1><abbr-2>J Neurosci</abbr-2></alt-periodical><pages>2369-2382</pages><volume>20</volume><number>6 <Go to ISI>://000085724200035</number><dates><year>2000</year><pub-dates><date>Mar 15</date></pub-dates></dates><accession-num>ISI:000085724200035</accession-num><urls></urls></record></Cite></EndNote>(Haber et al., 2000). Figure 2 about here3.2 The three phases of the learning process: acquisition, action-outcome and habit formation. The generalised arrangement of cortico-striatal loops and the heterogeniety of the striatum, as previously described, is functionally considered to reflect the three primary stages of learning. The initial ‘stamping’ in of behaviour, that makes the link between logged sensory and motor information as described in the previous section, is considered to occur at the level of both the ventral (nucleus accumbens) and dorsomedial (caudate) striatum PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZWRncmF2ZTwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+
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ADDIN EN.CITE.DATA (Yin and Knowlton, 2006; Redgrave et al., 2008). Activation of these cortico-striatal loops continue through the acquisition process but, once the behaviour has become learned, loops through the dorsomedial striatum start to predominate. This reflects a shift towards action-outcome learning where the animal, having learned the behaviour, maintains a process of closely monitoring the consequences of its actions in the context of expected outcome. The final stage of learning is habit formation, which occurs through a process of over-training where the animal has repeatedly received the same outcome for its actions. Neurophysiologically, this is associated with a dorso-lateral shift of cortico-striatal loops away from the caudate (DMS) towards the putamen (DLS). During action-outcome learning, both devaluation of the outcome or degradation of the contingency between the response and outcome, reduce the level of responding. During habit formation, however, responding becomes less affected by either of these manipulations as the animal diminishes it's monitoring of actions in terms of their outcome ADDIN EN.CITE <EndNote><Cite><Author>Haber</Author><Year>2009</Year><RecNum>4905</RecNum><IDText>The cortico-basal ganglia integrative network: The role of the thalamus</IDText><DisplayText>(Haber and Calzavara, 2009)</DisplayText><record><rec-number>4905</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820396">4905</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Haber, Suzanne N.</author><author>Calzavara, Roberta</author></authors></contributors><titles><title>The cortico-basal ganglia integrative network: The role of the thalamus</title><secondary-title>Brain Research Bulletin</secondary-title></titles><periodical><full-title>Brain Research Bulletin</full-title><abbr-1>Brain Res. Bull.</abbr-1><abbr-2>Brain Res Bull</abbr-2></periodical><pages>69-74</pages><volume>78</volume><number>2-3</number><dates><year>2009</year><pub-dates><date>Feb 16</date></pub-dates></dates><isbn>0361-9230</isbn><accession-num>WOS:000263431000004</accession-num><urls><related-urls><url><Go to ISI>://WOS:000263431000004</url></related-urls></urls><electronic-resource-num>10.1016/j.brainresbull.2008.09.013</electronic-resource-num></record></Cite></EndNote>(Haber and Calzavara, 2009).The fact that over-trained behaviours are more resistant to changes in contingency (from both a negative and positive reinforcement perspective) strongly suggests that there is less dopaminergic influence over the learning system during habit formation. Neurophysiological studies indicate that this is indeed the case PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XaWNrZW5zPC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48
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ADDIN EN.CITE.DATA (Wickens et al., 2007; Graybiel, 2008). However, all behaviours, no matter how ingrained they are through overtraining, will eventually be extinguished through lack of reinforcement and the dopamine-mediated physiological process of LTD (as previously described).Habit formation is critical during horse training because it can both facilitate and impede the learning process. For example, the ability to maintain a specific set of behavioural sequences without having to maintain dopaminergic-based reinforcement means, in practical terms, that aversive pressure can be removed from training whilst still maintaining the desired level of response. Similarly, habit formation can also be advantageous during positive reinforcement training. For example, one of the potential problems of positive reinforcement training programmes is the limit on work that an animal will perform in order to attain a non-essential resource (e.g. a reinforced sound such as a ‘click’ from a handheld device followed by a small amount of cereal-based concentrate) ADDIN EN.CITE <EndNote><Cite><Author>Dawkins</Author><Year>1991</Year><RecNum>705</RecNum><IDText>From an Animals Point-of-View - Motivation, Fitness, and Animal-Welfare</IDText><DisplayText>(Dawkins, 1991)</DisplayText><record><rec-number>705</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819873">705</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dawkins, M. S.</author></authors></contributors><titles><title>From an Animals Point-of-View - Motivation, Fitness, and Animal-Welfare</title><secondary-title>Behavioral and Brain Sciences</secondary-title><alt-title>Behav. Brain Sci.</alt-title><short-title>From an Animals Point-of-View - Motivation, Fitness, and Animal-Welfare</short-title></titles><periodical><full-title>Behavioral and Brain Sciences</full-title><abbr-1>Behav. Brain Sci.</abbr-1><abbr-2>Behav Brain Sci</abbr-2><abbr-3>Behavioral & Brain Sciences</abbr-3></periodical><alt-periodical><full-title>Behavioral and Brain Sciences</full-title><abbr-1>Behav. Brain Sci.</abbr-1><abbr-2>Behav Brain Sci</abbr-2><abbr-3>Behavioral & Brain Sciences</abbr-3></alt-periodical><pages>753-753</pages><volume>14</volume><number>4</number><dates><year>1991</year><pub-dates><date>Dec</date></pub-dates></dates><accession-num>ISI:A1991GX82700112</accession-num><urls></urls></record></Cite></EndNote>(Dawkins, 1991). Habit formation potentially circumnavigates this problem by allowing each incremental step of training (where the complexity and physical demand of the operant response is increasing) to be trained to a point where the animal is no longer monitoring the outcome (reward) of its action. To explain this in neurophysiological terms, habit formation means that dopaminergic reinforcement does not need to be cumulatively applied at each incremental step of the task. This allows work load to be increased without requiring a concurrent increase in the quantity of reward presented to the animal.The potential disadvantage of habit formation, however, is that in its extreme form it can reduce behavioural flexibility. The inability to shift from one learnt behaviour to another, often referred to as perseverance ADDIN EN.CITE <EndNote><Cite><Author>Garner</Author><Year>2006</Year><RecNum>2379</RecNum><IDText>Animal neuropsychology: Validation of the Intra-Dimensional Extra-Dimensional set shifting task for mice</IDText><DisplayText>(Garner et al., 2006)</DisplayText><record><rec-number>2379</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820111">2379</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Garner, J. P.</author><author>Thogerson, C. M.</author><author>Wurbel, H.</author><author>Murray, J. D.</author><author>Mench, J. A.</author></authors></contributors><titles><title>Animal neuropsychology: Validation of the Intra-Dimensional Extra-Dimensional set shifting task for mice</title><secondary-title>Behavioural Brain Research</secondary-title></titles><periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></periodical><pages>53-61</pages><volume>173</volume><number>1</number><dates><year>2006</year></dates><isbn>0166-4328</isbn><accession-num>WOS:000240652500007</accession-num><urls><related-urls><url><Go to ISI>://WOS:000240652500007</url></related-urls></urls><electronic-resource-num>10.1016/j.bbr.2006.06.002</electronic-resource-num></record></Cite></EndNote>(Garner et al., 2006), will mean that the animal cannot progress through the normal stages of successive training goals, as the complexity of the desired behavioural response is built up. Factors that can produce abnormally high perseverance and habit formation are discussed in section 4. 3.3 Neural mechanism underpinning negative reinforcement and punishmentTraining through negative reinforcement can inadvertently lead to the attenuation of other behavioural sequences through the physiological consequences of punishment. To give an example of this, a cue in the form of light non-aversive leg pressure to move the horse forward, may through insufficient training, not lead to the desired behaviour. A typical response to this by the rider is to increase leg pressure. This switches the stimulus from being a cue to being an aversive event which, has the potential to act both as a negative reinforcer and as a punisher. A negative reinforcer to produce the desired behaviour (in this example move forward) or as a punisher of a concurrent behaviour that the animal is currently engaged (for example, collected walk). The timing of increased and decreased dopamine release within the striatum during the different stages of this process potentially gives some insight to the processes involved. Although aversion-based learning processes are complex in terms of the types of neurons that are firing (and the different regions of the striatum involved during ADDIN EN.CITE <EndNote><Cite><Author>Wenzel</Author><Year>2015</Year><RecNum>5820</RecNum><IDText>A Role for Phasic Dopamine Release within the Nucleus Accumbens in Encoding Aversion: A Review of the Neurochemical Literature</IDText><DisplayText>(Wenzel et al., 2015)</DisplayText><record><rec-number>5820</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820475">5820</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wenzel, Jennifer M.</author><author>Rauscher, Noah A.</author><author>Cheer, Joseph F.</author><author>Oleson, Erik B.</author></authors></contributors><titles><title>A Role for Phasic Dopamine Release within the Nucleus Accumbens in Encoding Aversion: A Review of the Neurochemical Literature</title><secondary-title>Acs Chemical Neuroscience</secondary-title></titles><periodical><full-title>ACS Chemical Neuroscience</full-title><abbr-1>ACS Chem. Neurosci.</abbr-1><abbr-2>ACS Chem Neurosci</abbr-2></periodical><pages>16-26</pages><volume>6</volume><number>1</number><dates><year>2015</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1948-7193</isbn><accession-num>WOS:000348338900006</accession-num><urls><related-urls><url><Go to ISI>://WOS:000348338900006</url></related-urls></urls><electronic-resource-num>10.1021/cn500255p</electronic-resource-num></record></Cite></EndNote>(Wenzel et al., 2015), recent studies are starting to provide some clarification of the underlying mechanisms involved. For example, the application of unexpected aversive stimuli appears to consistently lead to the cessation or a reduction in the tonic firing rate of the mesoaccumbens dopamine pathway (VTA to NAc) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXRzdW1vdG88L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFy
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ADDIN EN.CITE.DATA (Matsumoto and Hikosaka, 2009; Cohen et al., 2012). This diminishes the strength of the neural link between the stimulus (whatever was occurring at that moment) and any behavioural sequence that was logged prior to, or during, the application of the aversive stimulus ADDIN EN.CITE <EndNote><Cite><Author>Tobler</Author><Year>2003</Year><RecNum>5107</RecNum><IDText>Coding of predicted reward omission by dopamine neurons in a conditioned inhibition paradigm</IDText><DisplayText>(Tobler et al., 2003)</DisplayText><record><rec-number>5107</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820418">5107</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tobler, P. N.</author><author>Dickinson, A.</author><author>Schultz, W.</author></authors></contributors><titles><title>Coding of predicted reward omission by dopamine neurons in a conditioned inhibition paradigm</title><secondary-title>Journal of Neuroscience</secondary-title></titles><periodical><full-title>Journal of Neuroscience</full-title><abbr-1>J. Neurosci.</abbr-1><abbr-2>J Neurosci</abbr-2></periodical><pages>10402-10410</pages><volume>23</volume><number>32</number><dates><year>2003</year><pub-dates><date>Nov 12</date></pub-dates></dates><isbn>0270-6474</isbn><accession-num>WOS:000186536100025</accession-num><urls><related-urls><url><Go to ISI>://WOS:000186536100025</url></related-urls></urls></record></Cite></EndNote>(Tobler et al., 2003). This process is similar to what occurs neurophysiologically when a reward is expected but not delivered (extinction) However, if that same aversive event is paired with a CS, the presentation of the CS, as an indicator of the aversive event to come, will lead to an increase in dopaminergic activity within the ventral striatum as a way of invigorating active avoidance behaviour in the animal (Young et al. 1993). Oleson et al. ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1"><Author>Oleson</Author><Year>2012</Year><RecNum>5897</RecNum><IDText>Subsecond Dopamine Release in the Nucleus Accumbens Predicts Conditioned Punishment and Its Successful Avoidance</IDText><DisplayText>(2012)</DisplayText><record><rec-number>5897</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820480">5897</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Oleson, Erik B.</author><author>Gentry, Ronny N.</author><author>Chioma, Vivian C.</author><author>Cheer, Joseph F.</author></authors></contributors><titles><title>Subsecond Dopamine Release in the Nucleus Accumbens Predicts Conditioned Punishment and Its Successful Avoidance</title><secondary-title>Journal of Neuroscience</secondary-title></titles><periodical><full-title>Journal of Neuroscience</full-title><abbr-1>J. Neurosci.</abbr-1><abbr-2>J Neurosci</abbr-2></periodical><pages>14804-14808</pages><volume>32</volume><number>42</number><dates><year>2012</year><pub-dates><date>Oct 17</date></pub-dates></dates><isbn>0270-6474</isbn><accession-num>WOS:000310054000032</accession-num><urls><related-urls><url><Go to ISI>://WOS:000310054000032</url></related-urls></urls><electronic-resource-num>10.1523/jneurosci.3087-12.2012</electronic-resource-num></record></Cite></EndNote>(2012) using a signalled operant shock avoidance task, trained animals to a conditioned stimulus (light) that indicated the arrival of an electric foot shock after a 2 second interval. A lever press during this 2 second interval resulted in the avoidance (non-presentation) of the foot shock. If the animal did not respond, recurring foot shocks were applied until the animal did respond with the lever press. Behaviourally, during the early stages of training, animals reverted to species-specific defence behaviour, which in the case of rodents was freezing behaviour, in response to both the application of the aversive stimulus and its conditioned cue. Physiologically, the early stage of training was associated with a drop in tonic dopamine release within the ventral striatum during both events. As training continued, the animals learned to stop the electric shock through lever pressing, and at this point of escape from the electric shock there was a surge in dopamine release within the ventral striatum. Finally, the animal learned to avoid the electric shock in advance by pressing the lever in response to the predicting cue. The transition to this final stage of learning was associated with a significant increase in dopamine release within the NAc at the point of cue presentation. The different effects of aversive stimuli when presented in different contexts are summarised in Figure 3. This study is extremely relevant to equitation and horse training as it closely mimics the typical sequences events during most training programmes, and thus, gives a potential insight to the neurophysiological processes involved. For example, the question asked at the beginning of this section was how the animal differentiates between negative reinforcement (to promote behaviour) and punishment (to suppress behaviour). At the level of dopamine physiology, it appears that the initial application of an aversive stimulus has the potential to suppress specific behaviours being performed at the point of aversive stimulus presentation. In rodents, this is an overall suppression of behaviour whereas for equids the species-specific defence response is predominately flight producing an overall increase in the level of behaviour. In this context, punishment in the horse has the paradoxical effect of simultaneously elevating general behaviours associated with flight, whilst at the same time suppressing specific behaviours performed at the time of the aversive stimulus presentation. The critical transition from punishment to negative reinforcement appears to occur as a result of repeated application of the aversive stimulus. This propagates trial and error behaviour as the animal attempts to escape the stimulus. Successful escape elicits dopamine release within the ventral striatum and this is the crucial point at which learning occurs during negative reinforcement ADDIN EN.CITE <EndNote><Cite><Author>Wenzel</Author><Year>2015</Year><RecNum>5820</RecNum><IDText>A Role for Phasic Dopamine Release within the Nucleus Accumbens in Encoding Aversion: A Review of the Neurochemical Literature</IDText><DisplayText>(Wenzel et al., 2015)</DisplayText><record><rec-number>5820</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820475">5820</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wenzel, Jennifer M.</author><author>Rauscher, Noah A.</author><author>Cheer, Joseph F.</author><author>Oleson, Erik B.</author></authors></contributors><titles><title>A Role for Phasic Dopamine Release within the Nucleus Accumbens in Encoding Aversion: A Review of the Neurochemical Literature</title><secondary-title>Acs Chemical Neuroscience</secondary-title></titles><periodical><full-title>ACS Chemical Neuroscience</full-title><abbr-1>ACS Chem. Neurosci.</abbr-1><abbr-2>ACS Chem Neurosci</abbr-2></periodical><pages>16-26</pages><volume>6</volume><number>1</number><dates><year>2015</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1948-7193</isbn><accession-num>WOS:000348338900006</accession-num><urls><related-urls><url><Go to ISI>://WOS:000348338900006</url></related-urls></urls><electronic-resource-num>10.1021/cn500255p</electronic-resource-num></record></Cite></EndNote>(Wenzel et al., 2015). If this process occurs in the context of a CS, dopamine release shifts temporally backwards to that point (as it does during positive reinforcement) to elicit and invigorate avoidance behaviour that prevents the onset of the aversive stimulus (Figure 2). .Further research is still required to elucidate the physiological consequences of different timings and duration of aversive stimuli. As stated at the outset of this discussion, switching between negative reinforcement and punishment can easily occur during the riding and training process. So, for example, what is happening physiologically when an operant response that is learned through negative reinforcement now elicits the presentation of an aversive stimulus? In the Oleson et al. (2012) study, this would be equivalent to, during the latter stages of training, presenting the electric shock in response to the lever press that normally allowed the animal to avoid the electric shock. Such switching from avoidance to punishment have previously been shown to have a dramatic effect of suppressing dopamine physiology and the general level of behaviour that the animal performs PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IaWtvc2FrYTwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+
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ADDIN EN.CITE.DATA (Hikosaka, 2010; Bressel and McNally, 2014). Although not well defined in the context of equine behaviour, the term ‘frozen watchfulness’ ,which describes emotional maltreatment in humans ADDIN EN.CITE <EndNote><Cite><Author>Walsh</Author><Year>1990</Year><RecNum>6731</RecNum><DisplayText>(Walsh, 1990)</DisplayText><record><rec-number>6731</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1455108106">6731</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Walsh, A.</author></authors></contributors><titles><title>Illegitimacy, child-abuse and neglect, and cognitive-development</title><secondary-title>Journal of Genetic Psychology</secondary-title></titles><periodical><full-title>Journal of Genetic Psychology</full-title><abbr-1>J. Genet. Psychol.</abbr-1><abbr-2>J Genet Psychol</abbr-2></periodical><pages>279-285</pages><volume>151</volume><number>3</number><dates><year>1990</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0022-1325</isbn><accession-num>WOS:A1990EH17800001</accession-num><urls><related-urls><url><Go to ISI>://WOS:A1990EH17800001</url></related-urls></urls></record></Cite></EndNote>(Walsh, 1990) has been used to describe some horses that are hyper-vigilant but unresponsive as a result of chronic exposure to negative reinforcement and punishment-orientated training schedules. It may be that perpetual shifts from negative reinforcement to punishment is the basis of this behavioural condition in horses. Overall, the studies discussed in this section highlight some of the risks of training under negative reinforcement systems and emphasise the critical importance of timing, where poor timing can lead to unexpected aversive stimuli becoming punishers that suppress rather than promote behaviour. Figure 3 about here4.0 Predictive markers of the neurophysiological and behavioural phenotypeThe term endophenotype describes the categorisation of an animal's behavioural traits in relation to its genetic profile ADDIN EN.CITE <EndNote><Cite><Author>John</Author><Year>1965</Year><RecNum>6004</RecNum><IDText>Genetic?speciation?in grasshopper eyprepocnemis plorans</IDText><DisplayText>(John and Lewis, 1965)</DisplayText><record><rec-number>6004</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820493">6004</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>John, B.</author><author>Lewis, K. R.</author></authors></contributors><titles><title>Genetic?speciation?in grasshopper eyprepocnemis plorans</title><secondary-title>Chromosoma</secondary-title></titles><periodical><full-title>Chromosoma</full-title><abbr-1>Chromosoma</abbr-1><abbr-2>Chromosoma</abbr-2></periodical><pages>308-&</pages><volume>16</volume><number>3</number><dates><year>1965</year><pub-dates><date>1965</date></pub-dates></dates><isbn>0009-5915</isbn><accession-num>WOS:A19656317500003</accession-num><urls><related-urls><url><Go to WoS>://WOS:A19656317500003</url></related-urls></urls><electronic-resource-num>10.1007/bf00325996</electronic-resource-num></record></Cite></EndNote>(John and Lewis, 1965). It describes the predisposition to express specific categories of normal and abnormal behaviour as a result of the genotype-environment interaction. For example, the trait of 'mood instability' is considered to be an endophenotype for attention deficit hyperactivity disorder (ADHD) in relation to specific polymorphic markers within the dopamine transporter gene gene DAT1 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZW9uZzwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (Jeong et al., 2015). In addition, the inability to differentiate different reward values of stimuli during a reward learning task is considered to be an endophenotype for depression (see Goldstein et al., 2014, for review). ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1" Hidden="1"><Author>Goldstein</Author><Year>2014</Year><RecNum>6006</RecNum><IDText>A review of selected candidate endophenotypes for depression</IDText><record><rec-number>6006</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820493">6006</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Goldstein, Brandon L.</author><author>Klein, Daniel N.</author></authors></contributors><titles><title>A review of selected candidate endophenotypes for depression</title><secondary-title>Clinical Psychology Review</secondary-title></titles><periodical><full-title>Clinical Psychology Review</full-title><abbr-1>Clin. Psychol. Rev.</abbr-1><abbr-2>Clin Psychol Rev</abbr-2></periodical><pages>417-427</pages><volume>34</volume><number>5</number><dates><year>2014</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0272-7358</isbn><accession-num>WOS:000341067500005</accession-num><urls><related-urls><url><Go to ISI>://WOS:000341067500005</url></related-urls></urls><electronic-resource-num>10.1016/j.cpr.2014.06.003</electronic-resource-num></record></Cite></EndNote> The concept of endophenotype is relatively unexplored in the horse but has huge potential to be developed given the behavioural profiling that can be easily undertaken and the affordable genetic testing that are now available. This would allow the behavioural effects of training and husbandry to be clearly defined in the context of genetic predisposition. For example, the consequence of different weaning strategies have been shown to have a large impact on the behaviour of some animals ADDIN EN.CITE <EndNote><Cite><Author>Waters</Author><Year>2002</Year><RecNum>1403</RecNum><IDText>Factors influencing the development of stereotypic and redirected behaviours in young horses: findings of a four year prospective epidemiological study</IDText><DisplayText>(Waters et al., 2002)</DisplayText><record><rec-number>1403</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819923">1403</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Waters, A. J.</author><author>Nicol, C. J.</author><author>French, N. P.</author></authors></contributors><titles><title>Factors influencing the development of stereotypic and redirected behaviours in young horses: findings of a four year prospective epidemiological study</title><secondary-title>Equine Veterinary Journal</secondary-title><alt-title>Equine Vet. J.</alt-title><short-title>Factors influencing the development of stereotypic and redirected behaviours in young horses: findings of a four year prospective epidemiological study</short-title></titles><periodical><full-title>Equine Veterinary Journal</full-title><abbr-1>Equine Vet. J.</abbr-1><abbr-2>Equine Vet J</abbr-2></periodical><alt-periodical><full-title>Equine Veterinary Journal</full-title><abbr-1>Equine Vet. J.</abbr-1><abbr-2>Equine Vet J</abbr-2></alt-periodical><pages>572-579</pages><volume>34</volume><number>6 <Go to ISI>://000178063800006</number><dates><year>2002</year><pub-dates><date>Sep</date></pub-dates></dates><accession-num>ISI:000178063800006</accession-num><urls></urls></record></Cite></EndNote>(Waters et al., 2002). The use of behavioural and genetic probes have the potential to identify susceptibility to this and other early-life event stressors. Furthermore, upregulation of dopamine systems can occur through consistent exposure to highly palatable substrates ADDIN EN.CITE <EndNote><Cite><Author>Colantuoni</Author><Year>2001</Year><RecNum>5398</RecNum><IDText>Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain</IDText><DisplayText>(Colantuoni et al., 2001)</DisplayText><record><rec-number>5398</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820437">5398</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Colantuoni, C.</author><author>Schwenker, J.</author><author>McCarthy, J.</author><author>Rada, P.</author><author>Ladenheim, B.</author><author>Cadet, J. L.</author><author>Schwartz, G. J.</author><author>Moran, T. H.</author><author>Hoebel, B. G.</author></authors></contributors><titles><title>Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain</title><secondary-title>Neuroreport</secondary-title></titles><periodical><full-title>Neuroreport</full-title><abbr-1>Neuroreport</abbr-1><abbr-2>Neuroreport</abbr-2></periodical><pages>3549-3552</pages><volume>12</volume><number>16</number><dates><year>2001</year><pub-dates><date>Nov 16</date></pub-dates></dates><isbn>0959-4965</isbn><accession-num>WOS:000172175000034</accession-num><urls><related-urls><url><Go to ISI>://WOS:000172175000034</url></related-urls></urls><electronic-resource-num>10.1097/00001756-200111160-00035</electronic-resource-num></record></Cite></EndNote>(Colantuoni et al., 2001), and this can have extensive ramifications on behaviour, as discussed in the previous sections. Again, the animal's predisposition to changes in neurophysiology and behaviour as a result of nutritional factors can be identified through behavioural and genetic markers.Table 1 presents a summary of current and potential behavioural/cognitive tests that can be applied to the horse in order to extract information about neurophysiological status and/or predisposition from the animal. These tests have been selected because the information that they provide is of potential relevance to the practical training and husbandry of the horse. In the following sections, we outline three of these tests and discuss their relevance from an applied perspective. This is followed by a review of current genetic markers that also have the potential to identify the equine endophenotype in a way that might be practically useful.4.1 Spontaneous blink rate As discussed, basal ganglia function and thus behavioural output, is profoundly influenced by DOPAMINE neurons originating in the midbrain. Therefore, any behavioural markers of DOPAMINE transmission will provide valuable insights into the neural basis of equine behaviour and cognition. Spontaneous Blink Rate (SBR) measurement is showing considerable promise in this regard. SBR is described as bilateral paroxysmal brief repetitive eye closures that occur continuously and in the absence of obvious external stimuli, and is not affected by external stimuli such as light, heat or humidity ADDIN EN.CITE <EndNote><Cite><Author>Karson</Author><Year>1983</Year><RecNum>2</RecNum><IDText>Spontaneous Eye-Blink Rates and Dopaminergic Systems</IDText><DisplayText>(Karson, 1983)</DisplayText><record><rec-number>2</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">2</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Karson, C.N.</author></authors></contributors><titles><title>Spontaneous Eye-Blink Rates and Dopaminergic Systems</title><secondary-title>Brain</secondary-title></titles><pages>643-653</pages><volume>106</volume><dates><year>1983</year></dates><urls></urls></record></Cite></EndNote>(Karson, 1983).Administration of dopamine agonists and antagonists has been used to validate the SBR as an indirect measure of dopamine tone within the CNS. For example, Karson (1983) administered 0.36mg/kg of the dopamine agonist apomorphine to four Rhesus Monkeys and observed a four-fold increase in SBR which could then be abolished following injection of the dopamine antagonist sulpiride. Therefore, elevated dopamine within the CNS increases spontaneous blinking whereas dopamine suppression has the opposite effect. Additional evidence for the use of SBR comes from human neurodegenerative disorders whereby depleted dopamine due to Parkinson’s disease will also lead to lowered SBR (Karson 1983). On the other hand, disorders resulting in dopamine facilitation (i.e schizophrenia) produce significant elevations in SBR ADDIN EN.CITE <EndNote><Cite><Author>Mackert</Author><Year>1991</Year><RecNum>3</RecNum><IDText>Increased blink rates in schizophrenics: influences of neuroleptics and psychopathology.</IDText><DisplayText>(Mackert et al., 1991)</DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mackert, A.</author><author>Fletcher, K.M.</author><author>Woyth, C.</author><author>Frick, K.</author></authors></contributors><titles><title>Increased blink rates in schizophrenics: influences of neuroleptics and psychopathology.</title><secondary-title><style face="italic" font="default" size="100%">Schizophrenia Research</style></secondary-title></titles><pages>41-47</pages><volume>4</volume><number>1</number><dates><year>1991</year></dates><urls></urls></record></Cite></EndNote>(Mackert et al., 1991). In relation to horses, neuro-degeneration of dopamine neurons terminating in the hypothalamus as a result of Cushings syndrome, is associated with significantly depressed SBR ADDIN EN.CITE <EndNote><Cite><Author>Stephenson</Author><Year>2014</Year><RecNum>4</RecNum><IDText>The use of eye blink rate (EBR) and changes in behaviour as potential early indicators of pituitary pars intermedia dysfunction in the horse.</IDText><DisplayText>(Stephenson et al., 2014)</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">4</key></foreign-keys><ref-type name="Conference Paper">47</ref-type><contributors><authors><author>Stephenson, B.</author><author>Hemmings, A.</author><author>Moore-Colyer, M.</author></authors></contributors><titles><title>The use of eye blink rate (EBR) and changes in behaviour as potential early indicators of pituitary pars intermedia dysfunction in the horse.</title><secondary-title>British Society of Animal Science, Annual Conference</secondary-title></titles><dates><year>2014</year></dates><pub-location>University of Nottingham</pub-location><urls></urls></record></Cite></EndNote>(Stephenson et al., 2014). Interestingly, Roberts et al. (2015) recorded lowered SBR in horses performing oral stereotypic behaviour (crib-biting). Post-mortem studies of crib-biting horses have demonstrated widespread alterations to dopamine function at the level of the striatum ADDIN EN.CITE <EndNote><Cite><Author>McBride</Author><Year>2005</Year><RecNum>55</RecNum><IDText>Altered mesoaccumbens and nigro-striatal dopamine physiology is associated with stereotypy development in a non-rodent species</IDText><DisplayText>(McBride and Hemmings, 2005)</DisplayText><record><rec-number>55</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819837">55</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McBride, S. D.</author><author>Hemmings, A.</author></authors></contributors><titles><title>Altered mesoaccumbens and nigro-striatal dopamine physiology is associated with stereotypy development in a non-rodent species</title><secondary-title>Behavioural Brain Research</secondary-title></titles><periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></periodical><pages>113-118</pages><volume>159</volume><number>1</number><dates><year>2005</year></dates><isbn>0166-4328</isbn><accession-num>WOS:000228509700014</accession-num><urls></urls><electronic-resource-num>10.1016/j.bbr.2004.10.014</electronic-resource-num></record></Cite></EndNote>(McBride and Hemmings, 2005), with evidence of significantly lowered dopamine transmission into the caudate, in tandem with up-regulated dopamine activity in the NAc. The SBR depression recorded by Roberts et al. (2015) would therefore appear to reflect the decreased activity in the caudate reported by McBride and Hemmings (2005) rather than the facilitation into the nucleus accumbens. In support of this notion, neural control of SBR depends on dopamine transmission from the substantia nigra ADDIN EN.CITE <EndNote><Cite><Author>Kaminer</Author><Year>2011</Year><RecNum>5</RecNum><IDText>Characterizing the Spontaneous Blink Generator: An Animal Model.</IDText><DisplayText>(Kaminer et al., 2011)</DisplayText><record><rec-number>5</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">5</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kaminer, J.</author><author>Powers, A.S.</author><author>Horn, K.G.</author><author>Hui, C.</author><author>Evinger, C.</author></authors></contributors><titles><title>Characterizing the Spontaneous Blink Generator: An Animal Model.</title><secondary-title>The Journal of Neuroscience</secondary-title></titles><pages>11256-11267</pages><volume>31</volume><number>31</number><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>(Kaminer et al., 2011), a midbrain region supplying dopamine exclusively to the caudate and putamen. SBR analysis in horses, therefore, has the potential to identify behavioural phenotypes in relation to stereotypy development. High levels of SBR in horses have is also associated with an inflexible approach to problem solving in a discrimination reversal task ADDIN EN.CITE <EndNote><Cite><Author>Hemmings</Author><Year>2012</Year><RecNum>6</RecNum><IDText>Equine Behavioural Neuroscience: research goals for the next decade and beyond</IDText><DisplayText>(Hemmings, 2012)</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">6</key></foreign-keys><ref-type name="Conference Paper">47</ref-type><contributors><authors><author>Hemmings, A.</author></authors></contributors><titles><title>Equine Behavioural Neuroscience: research goals for the next decade and beyond</title><secondary-title>International Society for Equitation Science, Annual Conference</secondary-title></titles><dates><year>2012</year></dates><pub-location>University of Edinburgh</pub-location><urls></urls></record></Cite></EndNote>(Hemmings, 2012). These findings are supported by rodent work that has demonstrated that elevated levels of dopamine results in accelerated habit formation in rats ADDIN EN.CITE <EndNote><Cite><Author>Nelson</Author><Year>2006</Year><RecNum>4</RecNum><IDText>Amphetamine exposure enhances habit formation</IDText><DisplayText>(Nelson and Killcross, 2006)</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819833">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nelson, A.</author><author>Killcross, S.</author></authors></contributors><titles><title>Amphetamine exposure enhances habit formation</title><secondary-title>Journal of Neuroscience</secondary-title></titles><periodical><full-title>Journal of Neuroscience</full-title><abbr-1>J. Neurosci.</abbr-1><abbr-2>J Neurosci</abbr-2></periodical><pages>3805-3812</pages><volume>26</volume><number>14</number><dates><year>2006</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0270-6474</isbn><accession-num>ISI:000236552400022</accession-num><urls></urls></record></Cite></EndNote>(Nelson and Killcross, 2006). As previously discussed in section 3.2, habit formation can be both advantageous and disadvantageous from a training perspective. Using SBR to identify animals with elevated dopamine, and thus predisposition to accelerated habitual responding, may lead to more a targeted application of repetition during training.4.2 Behavioural switching frequency The rate at which an animal transitions between behaviours (e.g. eating to standing alert to walking to eating) is referred to as Behaviour Switching Frequency (BSF). Used in tandem with measures of SBR, BSF measurements can provide additional insight into dopamine function at the level of the striatum. 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ADDIN EN.CITE.DATA (Robbins and Sahaikian, 1983; Cabib, 1993; Garner, 2006). Interestingly in a study in stereotypy horses ADDIN EN.CITE <EndNote><Cite><Author>Roberts</Author><Year>2015</Year><RecNum>6732</RecNum><DisplayText>(Roberts et al., 2015)</DisplayText><record><rec-number>6732</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1455787209">6732</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Roberts, Kirsty</author><author>Hemmings, Andrew</author><author>Moore-Colyer, Meriel</author><author>Hale, Catherine</author></authors></contributors><titles><title>Cognitive differences in horses performing locomotor versus oral stereotypic behaviour</title><secondary-title>Applied Animal Behaviour Science</secondary-title></titles><periodical><full-title>Applied Animal Behaviour Science</full-title><abbr-1>Appl. Anim. Behav. Sci.</abbr-1><abbr-2>Appl Anim Behav Sci</abbr-2></periodical><pages>37-44</pages><volume>168</volume><dates><year>2015</year></dates><publisher>Elsevier</publisher><isbn>0168-1591</isbn><urls><related-urls><url>;(Roberts et al., 2015) BSF was significantly elevated in both crib-biters and weavers compared to non-stereotypy performing controls, but only the crib-biting group displayed significant differences in the levels of SBR. This suggests neurophysiological differences between oral and locomotor stereotypy animals but also that two behavioural tests are measuring different neurophysiological aspects of basal ganglia function. Given the importance of striatal function to a spectrum of equine behavioural responses, as discussed in the previous sections, BSF and SBR are potential markers of both current and future behavioural phenotypes, for example, stress susceptibility, habit formation, flexible learning and stereotypy predisposition. Future research using these markers within longitudinal studies will allow the neurophysiological state of the animal to be tracked throughout its lift time in relation to key husbandry and management events. 4.3 Extinction Learning Paradigms and PerseveranceTo date, extinction learning paradigms have been employed to advance our understanding of neural dysfunction in animals performing stereotypic behaviour ADDIN EN.CITE <EndNote><Cite><Author>Garner</Author><Year>2002</Year><RecNum>1410</RecNum><IDText>Evidence for a relationship between cage stereotypies and behavioural disinhibition in laboratory rodents</IDText><DisplayText>(Garner and Mason, 2002)</DisplayText><record><rec-number>1410</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819924">1410</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Garner, J. P.</author><author>Mason, G. J.</author></authors></contributors><titles><title>Evidence for a relationship between cage stereotypies and behavioural disinhibition in laboratory rodents</title><secondary-title>Behavioural Brain Research</secondary-title><alt-title>Behav. Brain Res.</alt-title><short-title>Evidence for a relationship between cage stereotypies and behavioural disinhibition in laboratory rodents</short-title></titles><periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></periodical><alt-periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></alt-periodical><pages>83-92</pages><volume>136</volume><number>1 <Go to ISI>://000178776300009</number><dates><year>2002</year><pub-dates><date>Oct 17</date></pub-dates></dates><accession-num>ISI:000178776300009</accession-num><urls></urls></record></Cite></EndNote>(Garner and Mason, 2002) or in experimental scenarios that investigate substance addiction (Nelson and Killcross 2006). Although there is significant protocol variation between research groups, animals are generally taught a simple operant task (usually for a food / drug reward) followed by cessation of the reward to break down the action-outcome contingency. Response rate and or trials to extinction (cessation of operant responding) are then recorded as a measure of ‘perseverance’ ADDIN EN.CITE <EndNote><Cite><Author>Hemmings</Author><Year>2007</Year><RecNum>54</RecNum><IDText>Perseverative responding and the aetiology of equine oral stereotypy</IDText><DisplayText>(Hemmings et al., 2007)</DisplayText><record><rec-number>54</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819837">54</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hemmings, A.</author><author>McBride, S. D.</author><author>Hale, C. E.</author></authors></contributors><titles><title>Perseverative responding and the aetiology of equine oral stereotypy</title><secondary-title>Applied Animal Behaviour Science</secondary-title></titles><periodical><full-title>Applied Animal Behaviour Science</full-title><abbr-1>Appl. Anim. Behav. Sci.</abbr-1><abbr-2>Appl Anim Behav Sci</abbr-2></periodical><pages>143-150</pages><volume>104</volume><number>1-2</number><dates><year>2007</year></dates><isbn>0168-1591</isbn><accession-num>WOS:000245800300013</accession-num><urls></urls><electronic-resource-num>10.1016/j.applanim.2006.04.031</electronic-resource-num></record></Cite></EndNote>(Hemmings et al., 2007). In relation to stereotypic behaviour, bank voles performing high levels of oral stereotypy, were less likely to suppress a previously learned response in a spatial extinction paradigm (Garner and Mason 2002), a behavioural symptom that has been strongly linked to basal ganglia dysfunction in human patients with autism ADDIN EN.CITE <EndNote><Cite><Author>Turner</Author><Year>1997</Year><RecNum>1228</RecNum><IDText>Towards an executive dyfunction account of repetitive behaviour in autism</IDText><DisplayText>(Turner, 1997)</DisplayText><record><rec-number>1228</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819911">1228</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Turner, M.</author></authors><secondary-authors><author>Rusell, J.</author></secondary-authors></contributors><titles><title>Towards an executive dyfunction account of repetitive behaviour in autism</title><secondary-title>Autism as an executie disorder.</secondary-title><short-title>Towards an executive dyfunction account of repetitive behaviour in autism.</short-title></titles><pages>57-100</pages><dates><year>1997</year></dates><pub-location>New York</pub-location><publisher>Oxford University Press</publisher><urls></urls></record></Cite></EndNote>(Turner, 1997), and schizophrenia ADDIN EN.CITE <EndNote><Cite><Author>Frith</Author><Year>1983</Year><RecNum>269</RecNum><IDText>Stereotyped Responding By Schizophrenic-Patients On A 2-Choice Guessing Task</IDText><DisplayText>(Frith and Done, 1983)</DisplayText><record><rec-number>269</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819849">269</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Frith, C. D.</author><author>Done, D. J.</author></authors></contributors><titles><title>Stereotyped Responding By Schizophrenic-Patients On A 2-Choice Guessing Task</title><secondary-title>Psychological Medicine</secondary-title><short-title>Stereotyped Responding By Schizophrenic-Patients On A 2-Choice Guessing Task</short-title></titles><periodical><full-title>Psychological Medicine</full-title><abbr-1>Psychol. Med.</abbr-1><abbr-2>Psychol Med</abbr-2></periodical><pages>779-786</pages><volume>13</volume><number>4</number><dates><year>1983</year></dates><accession-num>ISI:A1983RW50500010</accession-num><urls><related-urls><url><Go to ISI>://A1983RW50500010</url></related-urls></urls></record></Cite></EndNote>(Frith and Done, 1983). More recently, similar impairments in extinction learning have also been recorded in stereotypy performing blue tits (Cyanistes caeruleus), marsh tits (Poecile palustris) ADDIN EN.CITE <EndNote><Cite><Author>Garner</Author><Year>2003</Year><RecNum>1483</RecNum><IDText>Stereotypies in caged parrots, schizophrenia and autism: evidence for a common mechanism</IDText><DisplayText>(Garner et al., 2003)</DisplayText><record><rec-number>1483</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819930">1483</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Garner, J. P.</author><author>Meehan, C. L.</author><author>Mench, J. A.</author></authors></contributors><titles><title>Stereotypies in caged parrots, schizophrenia and autism: evidence for a common mechanism</title><secondary-title>Behavioural Brain Research</secondary-title><alt-title>Behav. Brain Res.</alt-title><short-title>Stereotypies in caged parrots, schizophrenia and autism: evidence for a common mechanism</short-title></titles><periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></periodical><alt-periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></alt-periodical><pages>125-134</pages><volume>145</volume><number>1-2 <Go to ISI>://000186073300013</number><dates><year>2003</year><pub-dates><date>Oct 17</date></pub-dates></dates><accession-num>ISI:000186073300013</accession-num><urls></urls></record></Cite></EndNote>(Garner et al., 2003) and several species of bear ADDIN EN.CITE <EndNote><Cite><Author>Vickery</Author><Year>2005</Year><RecNum>1545</RecNum><IDText>Stereotypy and perseverative responding in caged bears: further data and analyses</IDText><DisplayText>(Vickery and Mason, 2005)</DisplayText><record><rec-number>1545</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819935">1545</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vickery, S. S.</author><author>Mason, G. J.</author></authors></contributors><titles><title>Stereotypy and perseverative responding in caged bears: further data and analyses</title><secondary-title>Applied Animal Behaviour Science</secondary-title><alt-title>Appl. Anim. Behav. Sci.</alt-title><short-title>Stereotypy and perseverative responding in caged bears: further data and analyses</short-title></titles><periodical><full-title>Applied Animal Behaviour Science</full-title><abbr-1>Appl. Anim. Behav. Sci.</abbr-1><abbr-2>Appl Anim Behav Sci</abbr-2></periodical><alt-periodical><full-title>Applied Animal Behaviour Science</full-title><abbr-1>Appl. Anim. Behav. Sci.</abbr-1><abbr-2>Appl Anim Behav Sci</abbr-2></alt-periodical><pages>247-260</pages><volume>91</volume><number>3-4</number><dates><year>2005</year><pub-dates><date>Jun</date></pub-dates></dates><accession-num>ISI:000229560100006</accession-num><urls><related-urls><url><Go to ISI>://000229560100006</url></related-urls></urls></record></Cite></EndNote>(Vickery and Mason, 2005), leading to the conclusion that stereotypy performance in captive animals is associated with altered basal ganglia output. In relation to equine stereotypy, Hemmings et al. (2007) subjected 10 crib-biting horses and 10 stereotypy free controls to a standard extinction learning paradigm. To summarise, all animals were taught to press a button for a food reward following the delivery of a conditioned stimulus (light and buzzer). Perseverance scores for the cribbing group were significantly higher compared to the control horses giving further support to the link between perseverance, basal ganglia dysfunction and stereotypy performance. Measures of perseverance also have the ability to predict predisposition to habit formation which, as discussed in section 3.2, is a critical factor in determining the animal’s aptitude for adaptability during learning and training. Tests that can measure learning adaptability, or predisposition to adaptability later on in the animal’s life, may therefore be advantageous. Extinction learning tasks, however, generally require the use of specialized operant devices to deliver conditioned stimuli and food rewards, in such a manner that body cues from the experimenter are eliminated. This equipment is generally not available commercially so considerable expertise is required during the design and construction phases. Consequently, probes featuring extinction learning will almost certainly fall beyond the means of the horse owner / trainer. This is unfortunate, as tests for habitual responding would be of use in order to prevent over-training, or as mentioned previously to identify animals predisposed to stereotypy development. Conversely, the equipment required to set up simple maze based experiments (fencing stakes and woven nylon tape) is cheap,and freely available at most equestrian establishments. Furthermore, the majority of protocols do not require a response shaping phase which translates to time-based savings and a decreased need for training expertise. At the time of writing, the use of maze tests to reveal alterations in equine brain function had not progressed beyond the Tolmans Place / Response task. Developed originally by Edward Tolman (1948), rats were trained to enter from the South and make a right turn for a food reward (see Figure 4a), this process is then repeated between 8 and 70 times ADDIN EN.CITE <EndNote><Cite><Author>Tolman</Author><Year>1949</Year><RecNum>5992</RecNum><IDText>Studies in spatial learning; place and response learning under different degrees of motivation</IDText><DisplayText>(Tolman and Gleitman, 1949)</DisplayText><record><rec-number>5992</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5992</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tolman, E. C.</author><author>Gleitman, H.</author></authors></contributors><titles><title>Studies in spatial learning; place and response learning under different degrees of motivation</title><secondary-title>Journal of experimental psychology</secondary-title></titles><periodical><full-title>Journal of Experimental Psychology</full-title><abbr-1>J. Exp. Psychol.</abbr-1><abbr-2>J Exp Psychol</abbr-2></periodical><pages>653-9</pages><volume>39</volume><number>5</number><dates><year>1949</year><pub-dates><date>1949-Oct</date></pub-dates></dates><isbn>0022-1015</isbn><accession-num>MEDLINE:15391108</accession-num><urls><related-urls><url><Go to ISI>://MEDLINE:15391108</url></related-urls></urls><electronic-resource-num>10.1037/h0059317</electronic-resource-num></record></Cite></EndNote>(Tolman and Gleitman, 1949). Figure 4 about hereA probe test is then conducted, to establish whether this well-practiced routine has progressed towards habit formation. Conducted only once, the probe test starts with the animal’s introduction into the North arm (see Figure 4b). An automatic right turn indicates progression into habit, also referred to as a ‘Response’ strategy. On the other hand, a left turn towards the pre-rewarded Easterly arm signals a ‘Place’ outcome. The latter suggesting to the experimenter that the animal is still deploying a more flexible non-habitual approach to the task. From a neural systems standpoint, activity of the caudate (dorsomedial striatum) is associated with flexible place learning, whilst the putamen (dorsolateral striatum) appears to mediate the habitual response ADDIN EN.CITE <EndNote><Cite><Author>Yin</Author><Year>2004</Year><RecNum>9</RecNum><IDText>Contributions of striatal subregions to place and response learning</IDText><DisplayText>(Yin and Knowlton, 2004)</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yin, H. H.</author><author>Knowlton, B. J.</author></authors></contributors><auth-address>Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095-1563, USA. hyin@ucla.edu</auth-address><titles><title>Contributions of striatal subregions to place and response learning</title><secondary-title>Learn Mem</secondary-title></titles><pages>459-63</pages><volume>11</volume><number>4</number><edition>2004/08/03</edition><keywords><keyword>Animals</keyword><keyword>Brain Mapping</keyword><keyword>Choice Behavior/ physiology</keyword><keyword>Male</keyword><keyword>Maze Learning/ physiology</keyword><keyword>N-Methylaspartate/physiology</keyword><keyword>Neostriatum/anatomy & histology/ physiology</keyword><keyword>Rats</keyword><keyword>Rats, Long-Evans</keyword><keyword>Spatial Behavior/ physiology</keyword></keywords><dates><year>2004</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>1072-0502 (Print)
1072-0502 (Linking)</isbn><accession-num>15286184</accession-num><urls></urls><custom2>498333</custom2><electronic-resource-num>10.1101/lm.81004 [doi]
11/4/459 [pii]</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Yin and Knowlton, 2004). Indeed, reversible and irreversible lesions of the dorsomedial striatum forces habitual responding, even in the absence of overtraining PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5ZaW48L0F1dGhvcj48WWVhcj4yMDA1PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA (Yin et al., 2005). Conversely, dorsolateral lesions prevent the formation of habit, despite multiple repetition ADDIN EN.CITE <EndNote><Cite><Author>Yin</Author><Year>2004</Year><RecNum>10</RecNum><IDText>Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning</IDText><DisplayText>(Yin et al., 2004)</DisplayText><record><rec-number>10</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">10</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yin, H. H.</author><author>Knowlton, B. J.</author><author>Balleine, B. W.</author></authors></contributors><auth-address>Department of Psychology, and Brain Research Institute, University of California, Los Angeles, 1285 Franz Hall, Los Angeles, CA 90095-1563, USA. hyin@ucla.edu</auth-address><titles><title>Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning</title><secondary-title>Eur J Neurosci</secondary-title></titles><pages>181-9</pages><volume>19</volume><number>1</number><edition>2004/01/31</edition><keywords><keyword>Animals</keyword><keyword>Behavior, Animal/physiology</keyword><keyword>Biofeedback, Psychology/physiology</keyword><keyword>Cognition/ physiology</keyword><keyword>Conditioning, Operant/physiology</keyword><keyword>Denervation</keyword><keyword>Extinction, Psychological/physiology</keyword><keyword>Female</keyword><keyword>Habits</keyword><keyword>Learning/ physiology</keyword><keyword>Male</keyword><keyword>Motivation</keyword><keyword>Neostriatum/drug effects/ physiology</keyword><keyword>Rats</keyword><keyword>Rats, Long-Evans</keyword><keyword>Reinforcement (Psychology)</keyword></keywords><dates><year>2004</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0953-816X (Print)
0953-816X (Linking)</isbn><accession-num>14750976</accession-num><urls></urls><electronic-resource-num>3095 [pii]</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Yin et al., 2004). A less pronounced analogue of dorsomedial inactivation is observable in the crib-biting horse, whereby post mortem evidence suggests significantly decreased dopamine neurotransmission into the caudate nucleus ADDIN EN.CITE <EndNote><Cite><Author>McBride</Author><Year>2005</Year><RecNum>55</RecNum><IDText>Altered mesoaccumbens and nigro-striatal dopamine physiology is associated with stereotypy development in a non-rodent species</IDText><DisplayText>(McBride and Hemmings, 2005)</DisplayText><record><rec-number>55</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819837">55</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McBride, S. D.</author><author>Hemmings, A.</author></authors></contributors><titles><title>Altered mesoaccumbens and nigro-striatal dopamine physiology is associated with stereotypy development in a non-rodent species</title><secondary-title>Behavioural Brain Research</secondary-title></titles><periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></periodical><pages>113-118</pages><volume>159</volume><number>1</number><dates><year>2005</year></dates><isbn>0166-4328</isbn><accession-num>WOS:000228509700014</accession-num><urls></urls><electronic-resource-num>10.1016/j.bbr.2004.10.014</electronic-resource-num></record></Cite></EndNote>(McBride and Hemmings, 2005). On this basis ADDIN EN.CITE <EndNote><Cite><Author>Parker</Author><Year>2009</Year><RecNum>1613</RecNum><IDText>Differential place and response learning in horses displaying an oral stereotypy</IDText><DisplayText>(Parker et al., 2009)</DisplayText><record><rec-number>1613</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819943">1613</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parker, Matthew</author><author>McBride, Sebastian D.</author><author>Redhead, Edward S.</author><author>Goodwin, Deborah</author></authors></contributors><titles><title>Differential place and response learning in horses displaying an oral stereotypy</title><secondary-title>Behavioural Brain Research</secondary-title></titles><periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></periodical><pages>100-105</pages><volume>200</volume><number>1</number><keywords><keyword>Horse</keyword><keyword>Stereotypy</keyword><keyword>Habit</keyword><keyword>Place/response</keyword></keywords><dates><year>2009</year></dates><isbn>0166-4328</isbn><urls><related-urls><url>;(Parker et al., 2009) hypothesized that crib-biting horses would align with the rodent studies (i.e Yin et al., 2005) and display a significant bias towards habitual responding, which indeed they did. These results suggest that maze testing is effective in identifying differential functioning of the dorsal striatum particularly in relation to accelerated habit formation. The use of maze tests may, therefore, be a simple and cheap, yet effective, marker for identifying learning and training adaptability in the horse. 4.4 Genetic predictors of the behavioural phenotype The current glut of unwanted horses in the UK, Ireland, Australia and United States is partly due to indiscriminate breeding bereft of targeted selection policy. However, with the sequencing of the equine genome in 2007, comes the opportunity to inform breeding strategy with genomic marker assisted selection. There now exists a handful of commercial enterprises devoted to the prediction of racing success based on markers of physicality such as muscle mass PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IaWxsPC9BdXRob3I+PFllYXI+MjAxMDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (Hill et al., 2010) and mitochondrial output ADDIN EN.CITE <EndNote><Cite><Author>Harrison</Author><Year>2006</Year><RecNum>12</RecNum><IDText>Mitochondrial DNA: an important female contribution to thoroughbred racehorse performance</IDText><DisplayText>(Harrison and Turrion-Gomez, 2006)</DisplayText><record><rec-number>12</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">12</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Harrison, S. P.</author><author>Turrion-Gomez, J. L.</author></authors></contributors><auth-address>Thoroughbred Genetics Ltd., Kent Science Park, Sittingbourne, Kent ME9 8AZ, UK. sph@</auth-address><titles><title>Mitochondrial DNA: an important female contribution to thoroughbred racehorse performance</title><secondary-title>Mitochondrion</secondary-title></titles><pages>53-63</pages><volume>6</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>DNA, Mitochondrial/ genetics</keyword><keyword>Female</keyword><keyword>Genes, Mitochondrial</keyword><keyword>Genetic Variation</keyword><keyword>Haplotypes</keyword><keyword>Horses/ genetics/ physiology</keyword><keyword>Pedigree</keyword><keyword>Phylogeny</keyword><keyword>Running</keyword><keyword>Sequence Analysis, DNA</keyword></keywords><dates><year>2006</year></dates><pub-location>Netherlands</pub-location><isbn>1567-7249 (Print)
1567-7249 (Linking)</isbn><accession-num>16516561</accession-num><urls></urls><electronic-resource-num>10.1016/j.mito.2006.01.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Harrison and Turrion-Gomez, 2006). Along with the physical components of athleticism, a suitably trainable and manageable temperament is required for fruitful propagation of the horse human bond. From a genetic standpoint, anecdotal reports from experienced horse handlers often apportion a heritable component to aspects of temperament, with certain stallions gaining notoriety based on unmanageable behavioural traits of their progeny. Over the past decade, some efforts have been made to reveal molecular predictors of temperament ADDIN EN.CITE <EndNote><Cite><Author>Momozawa</Author><Year>2005</Year><RecNum>13</RecNum><IDText>Association between equine temperament and polymorphisms in dopamine D4 receptor gene</IDText><DisplayText>(Momozawa et al., 2005)</DisplayText><record><rec-number>13</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">13</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Momozawa, Y.</author><author>Takeuchi, Y.</author><author>Kusunose, R.</author><author>Kikusui, T.</author><author>Mori, Y.</author></authors></contributors><auth-address>Laboratory of Veterinary Ethology, The University of Tokyo, 1-1-1 Yayoi, Tokyo, 113-8657, Japan</auth-address><titles><title>Association between equine temperament and polymorphisms in dopamine D4 receptor gene</title><secondary-title>Mamm Genome</secondary-title></titles><pages>538-44</pages><volume>16</volume><number>7</number><edition>2005/09/10</edition><keywords><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>DNA Primers</keyword><keyword>Horses/ genetics/physiology</keyword><keyword>Minisatellite Repeats/ genetics</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutation/genetics</keyword><keyword>Polymorphism, Single Nucleotide</keyword><keyword>Questionnaires</keyword><keyword>Receptors, Dopamine D4/ genetics</keyword><keyword>Sequence Analysis, DNA</keyword><keyword>Temperament/ physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0938-8990 (Print)
0938-8990 (Linking)</isbn><accession-num>16151699</accession-num><urls></urls><electronic-resource-num>10.1007/s00335-005-0021-3</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Momozawa et al., 2005) although it should be noted that this study area is still in its infancy. On the other hand, it could be argued that selection for temperament (albeit unwitting) has been ongoing from the point of domestication, whereby only those animals with suitably passive behavioural tendencies would lend themselves to initial recruitment and subsequent coping within early management systems ADDIN EN.CITE <EndNote><Cite><Author>Hemmings</Author><Year>2013</Year><RecNum>14</RecNum><IDText>From Dawn Horse to Racehorse</IDText><DisplayText>(Hemmings and Hale, 2013)</DisplayText><record><rec-number>14</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">14</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hemmings, A.</author><author>Hale, C.</author></authors></contributors><titles><title>From Dawn Horse to Racehorse</title><secondary-title>Equine Health</secondary-title></titles><pages>123-129</pages><volume>13</volume><number>10</number><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>(Hemmings and Hale, 2013). The longevity of any equine athlete will depend largely upon its ability to cope with restricted locomotion, social isolation as well as ad libitum feeding behaviour. Drawing from long established work in rodents, coping style indeed has a strong genetic component. Therefore, the aim of this section is to review the seminal works concerning equine behavioural genetics with a focus on coping style and traits with relevance to training and performance, such that future research efforts may be adequately informed. 4.5 Dopamine receptor genes in relation to temperament Human studies revealed a significant association between polymorphisms of the dopamine Receptor D4 (DRD4) locus, with traits such as novelty seeking and substance abuse ADDIN EN.CITE <EndNote><Cite><Author>Lusher</Author><Year>2001</Year><RecNum>15</RecNum><IDText>Dopamine D4 receptor gene (DRD4) is associated with Novelty Seeking (NS) and substance abuse: the saga continues</IDText><DisplayText>(Lusher et al., 2001)</DisplayText><record><rec-number>15</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">15</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lusher, J. M.</author><author>Chandler, C.</author><author>Ball, D.</author></authors></contributors><auth-address>Department of Psychology, London Guildhall University, Calcutta House, Old Castle Street, London E1 7NT, UK. lusher@lgu.ac.uk</auth-address><titles><title>Dopamine D4 receptor gene (DRD4) is associated with Novelty Seeking (NS) and substance abuse: the saga continues</title><secondary-title>Mol Psychiatry</secondary-title></titles><pages>497-9</pages><volume>6</volume><number>5</number><edition>2001/08/30</edition><keywords><keyword>Exploratory Behavior/ physiology</keyword><keyword>Humans</keyword><keyword>Personality</keyword><keyword>Receptors, Dopamine D2/ genetics</keyword><keyword>Receptors, Dopamine D4</keyword><keyword>Substance-Related Disorders/ genetics</keyword></keywords><dates><year>2001</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1359-4184 (Print)
1359-4184 (Linking)</isbn><accession-num>11526461</accession-num><urls></urls><electronic-resource-num>10.1038/sj.mp.4000918</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Lusher et al., 2001). This finding was the basis of a study by Momozawa et al. (2005) using a population of Japanese Thoroughbreds. In the 136 horses analysed, an A-G substitution was significantly associated with two temperament traits (curiosity and vigilance). Animals without the A allele had higher curiosity and lower vigilance scores, both of these behavioural tendencies could be argued as important traits in the training environment. Hyper-vigilance in particular, has been linked to inappropriate initiation of the flight response, in circumstances that might cause danger to human handlers, or undue energy expenditure within the stable. Increased curiosity, rather than neophobia, could be argued to be a desirable trait, when introducing na?ve animals to novel environments, maybe in the competition setting. Selection based on the A allele (either in parents or cohorts of young animals) might therefore lead to positive outcomes in competition and aspects of well-being linked to confinement.Other human research has also linked DRD4 polymorphisms to impulse control disorders, which are important as increased impulsivity is proposed to be a precursor of psychiatric illness, with behavioural inhibition data supporting the role of dopamine within impulsive control ADDIN EN.CITE <EndNote><Cite><Author>Congdon</Author><Year>2008</Year><RecNum>16</RecNum><IDText>Analysis of DRD4 and DAT polymorphisms and behavioral inhibition in healthy adults: implications for impulsivity</IDText><DisplayText>(Congdon et al., 2008)</DisplayText><record><rec-number>16</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">16</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Congdon, E.</author><author>Lesch, K. P.</author><author>Canli, T.</author></authors></contributors><auth-address>Department of Psychology, Stony Brook University, Stony Brook, New York 11794-2500, USA. econgdon@ic.sunysb.edu</auth-address><titles><title>Analysis of DRD4 and DAT polymorphisms and behavioral inhibition in healthy adults: implications for impulsivity</title><secondary-title>Am J Med Genet B Neuropsychiatr Genet</secondary-title></titles><pages>27-32</pages><volume>147B</volume><number>1</number><edition>2007/05/26</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Alleles</keyword><keyword>Dopamine Plasma Membrane Transport Proteins/ genetics</keyword><keyword>Female</keyword><keyword>Genetic Variation</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Impulsive Behavior/ genetics/psychology</keyword><keyword>Inhibition (Psychology)</keyword><keyword>Male</keyword><keyword>Polymorphism, Genetic</keyword><keyword>Receptors, Dopamine D4/ genetics</keyword></keywords><dates><year>2008</year><pub-dates><date>Jan 5</date></pub-dates></dates><isbn>1552-485X (Electronic)
1552-4841 (Linking)</isbn><accession-num>17525955</accession-num><urls></urls><electronic-resource-num>10.1002/ajmg.b.30557</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Congdon et al., 2008). From an equine perspective, impulse control will be an important behavioural facet during many handling applications, where the animal may be required to suppress a flight reaction. However, as the temperament trait impulsivity is a multifaceted trait including impaired response inhibition and response to novelty, so this must be considered when attempting to investigate the genetic origin of impulsivity. Nevertheless, those with a 7-repeat allele DRD4 polymorphism demonstrated significant impairment during a Stop Signal task thereby demonstrating impulsivity (Congdon et al. 2008). Once again this demonstrates the impact dopamine receptor genetics have on temperament traits, and could indeed provide insights into cognitive function through the development of both behavioural and genetic markers in the horse. 4.6 Genetic basis of stress coping strategyFor a gregarious herbivore, commonly applied horse management strategies such as restricted forage intake and movement, are often perceived as stressful, leading to activation of behavioural coping strategies, which in other species appear to be under a degree of genetic control. Much of the work to date features two inbred genetically distinct strains of mice, the DBA/2 and C57/b ADDIN EN.CITE <EndNote><Cite><Author>Cabib</Author><Year>2006</Year><RecNum>5129</RecNum><IDText>The neurobiology of stereotypy II: The role of stress</IDText><DisplayText>(Cabib, 2006)</DisplayText><record><rec-number>5129</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820419">5129</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Cabib,S.</author></authors><secondary-authors><author>Mason,G.</author><author>Rushen,J.</author></secondary-authors></contributors><titles><title>The neurobiology of Stereotypy II: the role of stress.</title><secondary-title>Stereotypic Animal Behaviour: Fundamentals and Applications to Welfare?</secondary-title></titles><pages>227-248</pages><section>8</section><dates><year>2006</year></dates><pub-location>Wallingford, Oxfordshire.</pub-location><publisher>CABI</publisher><urls></urls></record></Cite></EndNote>(Cabib, 2006). In response to stressors such as social isolation, the former deploys what is referred to as the active response, characterised by hyper-locomotion and stereotypy, the latter behavioural depression featuring reduced activity ADDIN EN.CITE <EndNote><Cite><Author>Cabib</Author><Year>2012</Year><RecNum>17</RecNum><IDText>Learning to cope with stress: psychobiological mechanisms of stress resilience</IDText><DisplayText>(Cabib et al., 2012)</DisplayText><record><rec-number>17</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">17</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cabib, S.</author><author>Campus, P.</author><author>Colelli, V.</author></authors></contributors><auth-address>Department of Psychology, Sapienza University of Rome, Italy, Rome. Simona.cabib@uniroma1.it</auth-address><titles><title>Learning to cope with stress: psychobiological mechanisms of stress resilience</title><secondary-title>Rev Neurosci</secondary-title></titles><pages>659-72</pages><volume>23</volume><number>5-6</number><edition>2012/11/20</edition><keywords><keyword>Adaptation, Psychological</keyword><keyword>Animals</keyword><keyword>Conditioning, Operant</keyword><keyword>Disease Models, Animal</keyword><keyword>Dopamine/metabolism</keyword><keyword>Endophenotypes</keyword><keyword>Learning/ physiology</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Inbred DBA</keyword><keyword>Neuronal Plasticity/physiology</keyword><keyword>Nucleus Accumbens/metabolism</keyword><keyword>Species Specificity</keyword><keyword>Stress, Psychological/pathology/ physiopathology</keyword><keyword>Swimming</keyword></keywords><dates><year>2012</year></dates><isbn>0334-1763 (Print)
0334-1763 (Linking)</isbn><accession-num>23159866</accession-num><urls></urls><electronic-resource-num>10.1515/revneuro-2012-0080</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Cabib et al., 2012). From a neural standpoint, the active strategy results from increased dopamine transmission into the nucleus accumbens, whilst the passive features decreased release of this neurotransmitter ADDIN EN.CITE <EndNote><Cite><Author>Cabib</Author><Year>1997</Year><RecNum>1181</RecNum><IDText>Parallel strain-dependent susceptibility to environmentally- induced stereotypies and stress-induced behavioral sensitization in mice</IDText><DisplayText>(Cabib and Bonaventura, 1997)</DisplayText><record><rec-number>1181</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819908">1181</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cabib, S.</author><author>Bonaventura, N.</author></authors></contributors><titles><title>Parallel strain-dependent susceptibility to environmentally- induced stereotypies and stress-induced behavioral sensitization in mice</title><secondary-title>Physiology & Behavior</secondary-title><short-title>Parallel strain-dependent susceptibility to environmentally- induced stereotypies and stress-induced behavioral sensitization in mice</short-title></titles><periodical><full-title>Physiology & Behavior</full-title><abbr-1>Physiol. Behav.</abbr-1><abbr-2>Physiol Behav</abbr-2></periodical><pages>499-506</pages><volume>61</volume><dates><year>1997</year></dates><label>727</label><urls></urls></record></Cite></EndNote>(Cabib and Bonaventura, 1997). Interestingly, horses with active coping tendencies appear to experience similar elevations in dopamine transmission, thus, there appears to also be a link between active coping individuals of this species and stereotypy predisposition ADDIN EN.CITE <EndNote><Cite><Author>Bachmann</Author><Year>2003</Year><RecNum>1452</RecNum><DisplayText>(Bachmann et al., 2003)</DisplayText><record><rec-number>1452</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819927">1452</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bachmann, I.</author><author>Audige, L.</author><author>Stauffacher, M.</author></authors></contributors><titles><title>Risk factors associated with behavioural disorders of crib- biting, weaving and box-walking in Swiss horses</title><secondary-title>Equine Veterinary Journal</secondary-title><alt-title>Equine Vet. J.</alt-title><short-title>Risk factors associated with behavioural disorders of crib- biting, weaving and box-walking in Swiss horses</short-title></titles><periodical><full-title>Equine Veterinary Journal</full-title><abbr-1>Equine Vet. J.</abbr-1><abbr-2>Equine Vet J</abbr-2></periodical><alt-periodical><full-title>Equine Veterinary Journal</full-title><abbr-1>Equine Vet. J.</abbr-1><abbr-2>Equine Vet J</abbr-2></alt-periodical><pages>158-163</pages><volume>35</volume><number>2 <Go to ISI>://000181583700009</number><dates><year>2003</year><pub-dates><date>Mar</date></pub-dates></dates><accession-num>ISI:000181583700009</accession-num><urls></urls></record></Cite></EndNote>(Bachmann et al., 2003). Moreover, recent behavioural probes of dopamine activity (spontaneous eye blink rate and behaviour initiation frequency) revealed strong evidence for elevated dopamine in horses performing both oral and locomotor stereotypy ADDIN EN.CITE <EndNote><Cite><Author>Roberts</Author><Year>2015</Year><RecNum>6732</RecNum><DisplayText>(Roberts et al., 2015)</DisplayText><record><rec-number>6732</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1455787209">6732</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Roberts, Kirsty</author><author>Hemmings, Andrew</author><author>Moore-Colyer, Meriel</author><author>Hale, Catherine</author></authors></contributors><titles><title>Cognitive differences in horses performing locomotor versus oral stereotypic behaviour</title><secondary-title>Applied Animal Behaviour Science</secondary-title></titles><periodical><full-title>Applied Animal Behaviour Science</full-title><abbr-1>Appl. Anim. Behav. Sci.</abbr-1><abbr-2>Appl Anim Behav Sci</abbr-2></periodical><pages>37-44</pages><volume>168</volume><dates><year>2015</year></dates><publisher>Elsevier</publisher><isbn>0168-1591</isbn><urls><related-urls><url>;(Roberts et al., 2015). Taken together, it would appear that the neural correlates of active coping style at least, are common to both equine and murine systems. When considering issues of ethological survivability, for free living equids, the active style is likely to be more effective, especially considering the open expanses of space occupied by feral horses. In such a niche, behavioural depression in the face of predation stress would lead to death. However, for species relying upon stillness and camouflage in dense foliage the passive style is likely to be more appropriate. Furthermore, and through the ocular of domestic management, passive tendencies would be of potential benefit, even to a species like the horse due to the long periods of inactivity and movement restriction often imposed. As such, genetic probing of coping style warrants further research effort, in view of developing genomic tools of prediction. With this in mind, and given the linkage between stereotypy and active coping, Hemmann et al. ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1"><Author>Hemmann</Author><Year>2014</Year><RecNum>18</RecNum><IDText>Exploration of known stereotypic behaviour-related candidate genes in equine crib-biting</IDText><DisplayText>(2014)</DisplayText><record><rec-number>18</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">18</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Hemmann, K.</author><author>Ahonen, S.</author><author>Raekallio, M.</author><author>Vainio, O.</author><author>Lohi, H.</author></authors></contributors><auth-address>1Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Koetilantie 7, P.O. Box 57, 00014 Helsinki, Finland.
2 Department of Veterinary Biosciences and Research Programs Unit, Molecular Neurology, University of Helsinki, Finland and the Folkhalsan Institute of Genetics, Finland.</auth-address><titles><title>Exploration of known stereotypic behaviour-related candidate genes in equine crib-biting</title><secondary-title>Animal</secondary-title></titles><pages>347-53</pages><volume>8</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Behavior, Animal</keyword><keyword>Female</keyword><keyword>Genetic Predisposition to Disease</keyword><keyword>Horses/ genetics/physiology</keyword><keyword>Male</keyword><keyword>Peptide Hormones/ genetics</keyword><keyword>Polymorphism, Single Nucleotide</keyword><keyword>Receptors, Peptide/ genetics</keyword><keyword>Stereotyped Behavior</keyword></keywords><dates><year>2014</year></dates><pub-location>England</pub-location><isbn>1751-732X (Electronic)
1751-7311 (Linking)</isbn><accession-num>24387899</accession-num><urls></urls><electronic-resource-num>10.1017/s1751731113002346</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(2014) investigated gene targets linked to crib-biting, including polymorphisms with close proximity to the D1 dopamine receptor gene (DRD1) and actual coding regions of the mu-opioid receptor gene (OPRM1). No associations were uncovered in this study, although more detailed analysis of coding regions of the DRD1 gene have revealed a cytosine deletion with an 80% prediction efficiency with regards to the crib-biting phenotype ADDIN EN.CITE <EndNote><Cite><Author>Hemmings</Author><Year>2012</Year><RecNum>6</RecNum><IDText>Equine Behavioural Neuroscience: research goals for the next decade and beyond</IDText><DisplayText>(Hemmings, 2012)</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">6</key></foreign-keys><ref-type name="Conference Paper">47</ref-type><contributors><authors><author>Hemmings, A.</author></authors></contributors><titles><title>Equine Behavioural Neuroscience: research goals for the next decade and beyond</title><secondary-title>International Society for Equitation Science, Annual Conference</secondary-title></titles><dates><year>2012</year></dates><pub-location>University of Edinburgh</pub-location><urls></urls></record></Cite></EndNote>(Hemmings, 2012). The later study however, featured a small study cohort (n=20) and so these data are of limited significance and further work is certainly required. Furthermore, the candidate gene approach to mutation detection has been superseded in recent years by techniques such as the Genome Wide Association Study (GWAS), which enables more holistic investigation of the genome. Undoubtedly, modalities such as this will offer significantly greater chances of uncovering genetic differences should they exist. Of course, should a genetic test for aspects of active coping ever be made available, consideration is warranted with regards to its application. This factor is particularly relevant to the production of horses for disciplines such as racing and eventing, which may partly rely upon active coping tendencies for competition success. For example, crib-biting and weaving animals were recently shown to acquire a simple operant learning task significantly faster than stereotypy free controls (Roberts et al. 2015). Furthermore, top riders positively select for active coping tendencies ADDIN EN.CITE <EndNote><Cite><Author>Hemmings</Author><Year>2011</Year><RecNum>6003</RecNum><IDText>Fueling Bad Habits</IDText><DisplayText>(Hemmings, 2011)</DisplayText><record><rec-number>6003</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820493">6003</key></foreign-keys><ref-type name="Magazine Article">19</ref-type><contributors><authors><author>Hemmings, A</author></authors></contributors><titles><title>Fueling Bad Habits</title><secondary-title>Horse and Hound</secondary-title></titles><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>(Hemmings, 2011). Therefore, given the negative perception of stereotypy performance in the horse owning populace ADDIN EN.CITE <EndNote><Cite><Author>McBride</Author><Year>2001</Year><RecNum>1349</RecNum><IDText>The perception and subsequent management of equine stereotypic behaviour by horse owners; implications for animal welfare</IDText><DisplayText>(McBride and Long, 2001)</DisplayText><record><rec-number>1349</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819919">1349</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McBride, S.D.</author><author>Long, L.</author></authors></contributors><titles><title>The perception and subsequent management of equine stereotypic behaviour by horse owners; implications for animal welfare</title><secondary-title>Veterinary Record</secondary-title><alt-title>Vet Rec</alt-title><short-title>The perception and subsequent management of equine stereotypic behaviour by horse owners; implications for animal welfare.</short-title></titles><periodical><full-title>Veterinary Record</full-title><abbr-1>Vet. Rec.</abbr-1><abbr-2>Vet Rec</abbr-2></periodical><alt-periodical><full-title>Veterinary Record</full-title><abbr-1>Vet Rec</abbr-1><abbr-2>Vet. Rec</abbr-2></alt-periodical><pages>799-802</pages><volume>148</volume><number>26</number><dates><year>2001</year></dates><label>1052</label><urls></urls></record></Cite></EndNote>(McBride and Long, 2001), undue selection against active coping in an effort to banish stereotypy could lead to reductions in trainability and in turn performance. 4.7 Genomic predictors of aggression The herd structure of feral equids features various mechanisms geared towards avoidance of con-specific aggression PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OdW5lejwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (Nunez et al., 2014). Furthermore, even in the face of predation, the horse evolved coping tools favour flight rather than fight. That said, in the domestic setting some animals deploy inappropriate/unwanted instances of aggression that increase injury risk to handlers and other horses. Therefore, genomic predictors of aggression may be useful, particularly when animals are required for disciplines such as Equine Assisted Therapy (EAT) where unpredictable and threatening output from human subjects are commonplace. Functional deletion of the tryptophan hydroxylase (TPH) gene from the murine genome leads to a hyper-aggressive phenotype ADDIN EN.CITE <EndNote><Cite><Author>Mosienko</Author><Year>2012</Year><RecNum>20</RecNum><IDText>Exaggerated aggression and decreased anxiety in mice deficient in brain serotonin</IDText><DisplayText>(Mosienko et al., 2012)</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">20</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Mosienko, V.</author><author>Bert, B.</author><author>Beis, D.</author><author>Matthes, S.</author><author>Fink, H.</author><author>Bader, M.</author><author>Alenina, N.</author></authors></contributors><auth-address>Department of Molecular Biology of Peptide Hormones, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.</auth-address><titles><title>Exaggerated aggression and decreased anxiety in mice deficient in brain serotonin</title><secondary-title>Transl Psychiatry</secondary-title></titles><pages>e122</pages><volume>2</volume><keywords><keyword>Aggression/ physiology/psychology</keyword><keyword>Agonistic Behavior/physiology</keyword><keyword>Animals</keyword><keyword>Anxiety/ genetics/ physiopathology</keyword><keyword>Brain/ physiopathology</keyword><keyword>Depression/genetics/physiopathology</keyword><keyword>Female</keyword><keyword>Heterozygote Detection</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Phenotype</keyword><keyword>Serotonin/ deficiency/physiology</keyword><keyword>Tryptophan Hydroxylase/deficiency/genetics</keyword></keywords><dates><year>2012</year></dates><pub-location>United States</pub-location><isbn>2158-3188 (Electronic)
2158-3188 (Linking)</isbn><accession-num>22832966</accession-num><urls></urls><electronic-resource-num>10.1038/tp.2012.44</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Mosienko et al., 2012) whilst polymorphisms of this locus lead to aggressive tendencies in humans PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aYWxzbWFuPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (Zalsman et al., 2011). Tryptophan hydroxylase is the rate-limiting enzyme in the biosynthetic pathway responsible for the conversion of tryptophan into serotonin (a key neurotransmitter which plays a role in reward and emotional stability) ADDIN EN.CITE <EndNote><Cite><Author>Carlson</Author><Year>2001</Year><RecNum>1361</RecNum><DisplayText>(Carlson, 2001)</DisplayText><record><rec-number>1361</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819920">1361</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Carlson, N., R.</author></authors></contributors><titles><title>Physiology of behavior</title><short-title>Physiology of behavior</short-title></titles><edition>7</edition><dates><year>2001</year></dates><pub-location>Boston</pub-location><publisher>Allyn and Bacon</publisher><urls></urls></record></Cite></EndNote>(Carlson, 2001). Knockout strategies such as that undertaken by Mosienko et al., ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1"><Author>Mosienko</Author><Year>2012</Year><RecNum>20</RecNum><DisplayText>(2012)</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">20</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Mosienko, V.</author><author>Bert, B.</author><author>Beis, D.</author><author>Matthes, S.</author><author>Fink, H.</author><author>Bader, M.</author><author>Alenina, N.</author></authors></contributors><auth-address>Department of Molecular Biology of Peptide Hormones, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.</auth-address><titles><title>Exaggerated aggression and decreased anxiety in mice deficient in brain serotonin</title><secondary-title>Transl Psychiatry</secondary-title></titles><pages>e122</pages><volume>2</volume><keywords><keyword>Aggression/ physiology/psychology</keyword><keyword>Agonistic Behavior/physiology</keyword><keyword>Animals</keyword><keyword>Anxiety/ genetics/ physiopathology</keyword><keyword>Brain/ physiopathology</keyword><keyword>Depression/genetics/physiopathology</keyword><keyword>Female</keyword><keyword>Heterozygote Detection</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Phenotype</keyword><keyword>Serotonin/ deficiency/physiology</keyword><keyword>Tryptophan Hydroxylase/deficiency/genetics</keyword></keywords><dates><year>2012</year></dates><pub-location>United States</pub-location><isbn>2158-3188 (Electronic)
2158-3188 (Linking)</isbn><accession-num>22832966</accession-num><urls></urls><electronic-resource-num>10.1038/tp.2012.44</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(2012) commonly lead to a 98% reduction in brain serotonin levels, a neurochemical imbalance that is believed to underlie the recorded increase in impulsive aggression. Building on findings such as this, Momozawa et al. ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1"><Author>Momozawa</Author><Year>2005</Year><RecNum>13</RecNum><DisplayText>(2005)</DisplayText><record><rec-number>13</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">13</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Momozawa, Y.</author><author>Takeuchi, Y.</author><author>Kusunose, R.</author><author>Kikusui, T.</author><author>Mori, Y.</author></authors></contributors><auth-address>Laboratory of Veterinary Ethology, The University of Tokyo, 1-1-1 Yayoi, Tokyo, 113-8657, Japan</auth-address><titles><title>Association between equine temperament and polymorphisms in dopamine D4 receptor gene</title><secondary-title>Mamm Genome</secondary-title></titles><pages>538-44</pages><volume>16</volume><number>7</number><edition>2005/09/10</edition><keywords><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>DNA Primers</keyword><keyword>Horses/ genetics/physiology</keyword><keyword>Minisatellite Repeats/ genetics</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutation/genetics</keyword><keyword>Polymorphism, Single Nucleotide</keyword><keyword>Questionnaires</keyword><keyword>Receptors, Dopamine D4/ genetics</keyword><keyword>Sequence Analysis, DNA</keyword><keyword>Temperament/ physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0938-8990 (Print)
0938-8990 (Linking)</isbn><accession-num>16151699</accession-num><urls></urls><electronic-resource-num>10.1007/s00335-005-0021-3</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(2005) initiated the search for naturally occurring TPH2 mutations in equine populations, this limited study found no significant association with polymorphic regions of this gene and aggressive tendencies, in agreement with findings from our laboratory ADDIN EN.CITE <EndNote><Cite><Author>Hemmings</Author><Year>2012</Year><RecNum>6</RecNum><IDText>Equine Behavioural Neuroscience: research goals for the next decade and beyond</IDText><DisplayText>(Hemmings, 2012)</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">6</key></foreign-keys><ref-type name="Conference Paper">47</ref-type><contributors><authors><author>Hemmings, A.</author></authors></contributors><titles><title>Equine Behavioural Neuroscience: research goals for the next decade and beyond</title><secondary-title>International Society for Equitation Science, Annual Conference</secondary-title></titles><dates><year>2012</year></dates><pub-location>University of Edinburgh</pub-location><urls></urls></record></Cite></EndNote>(Hemmings, 2012). Drawing once again from better studied species, polymorphic variants at a range of additional gene targets (including the D2 dopamine receptor [DRD2] locus) have been identified as contributory to hyper aggression ADDIN EN.CITE <EndNote><Cite><Author>Butovskaya</Author><Year>2013</Year><RecNum>22</RecNum><IDText>Aggression and polymorphisms in AR, DAT1, DRD2, and COMT genes in Datoga pastoralists of Tanzania</IDText><DisplayText>(Butovskaya et al., 2013)</DisplayText><record><rec-number>22</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018486">22</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Butovskaya, M. L.</author><author>Vasilyev, V. A.</author><author>Lazebny, O. E.</author><author>Suchodolskaya, E. M.</author><author>Shibalev, D. V.</author><author>Kulikov, A. M.</author><author>Karelin, D. V.</author><author>Burkova, V. N.</author><author>Mabulla, A.</author><author>Ryskov, A. P.</author></authors></contributors><auth-address>1] Department of Cross-Cultural Psychology and Human Ethology, Institute of Ethnology and Anthropology, Russian Academy of Sciences, Moscow, 119991, Russia [2].</auth-address><titles><title>Aggression and polymorphisms in AR, DAT1, DRD2, and COMT genes in Datoga pastoralists of Tanzania</title><secondary-title>Sci Rep</secondary-title></titles><pages>3148</pages><volume>3</volume><dates><year>2013</year></dates><pub-location>England</pub-location><isbn>2045-2322 (Electronic)
2045-2322 (Linking)</isbn><accession-num>24193094</accession-num><urls></urls><electronic-resource-num>10.1038/srep03148</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Butovskaya et al., 2013), and thus the search for equine gene targets should undoubtedly be widened accordingly, preferably via GWAS. 5.0 Conclusions and areas for future research. Understanding the mechanisms underpinning behaviour brings additional understanding about the behaviour itself. In particular, it provides a better awareness of how factors can affect behaviour, from the interaction of genes and environment, through to specific events such as the application of an aversive stimulus. Practically, this allows further optimisation of training techniques and the opportunity to improve the husbandry of the horse.The neurotransmitter dopamine has featured heavily in this review. This reflects its pivotal role in the underlying mechanisms of learning and how it directs and motivates the animal towards positive resources and away from potentially harmful aversive stimuli. Dopamine is also crucial in determining the day-today welfare of the animal. Up-regulation of dopamine, as a result of environmental factors such as nutrition or early life stressors, can produce a hyper-motivated phenotype. These individuals are unable to attain their highly motivated goals due to the restrictive nature of the stable environment. This increases stress levels of the animals and is also the potential basis for stereotypy development. Down-regulation of dopamine, also as a result of stress, can lead to behavioural depression.This review has highlighted the use of non-invasive methods for assessing dopaminergic tone in the animal as well as more general cognitive tests for monitoring specific psychological traits, such as impulsivity and behavioural inflexibility, that may be useful from a practical perspective. Many of the tests listed in Table 1 have been validated in the horse and thus provide the basis for future longitudinal testing to assess how husbandry factors affect the psychological state of the animal. More importantly, it provides an empirical method to formally test how neurophysiological state (and behaviour) can be modulated through specific equine husbandry strategies, in in a way that is both beneficial to the animal’s welfare as well as its performance ability. References ADDIN EN.REFLIST Aosaki, T., Kiuchi, K., Kawaguchi, Y., 1998. 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Sensorimotor Cortex (SMC) Association Cortices (AC) Pre-Frontal Cortex (PFC) Caudatus (C) Putamen (P) Nucleus Accumbens (NA) Ventral Tegmental Area (VTA) Amygdala (Amyg) Hippocampus (HC)Globus Pallidus internal and external segments (GPi and GPe) Substantia Nigra pars compacta and pars reticulata (SNpc and SNpr) Sub Thalamic Nucleus (STN) Thalamus (Thal) Ventral pallidum (VP).Figure 2. Changes in phasic dopamine concentration (nM) within the striatum as a result of unexpected reward during early training and the presentation of a conditioned stimulus during late training. Note the lack of dopamine response during an expected reward PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5ManVuZ2Jlcmc8L0F1dGhvcj48WWVhcj4xOTkyPC9ZZWFy
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ADDIN EN.CITE.DATA (Oleson et al., 2012; Wenzel et al., 2015).Figure 4. Place response task incorporating the cross maze. During the training phase (a) rats are trained to enter the south entrance followed by a right turn to retrieve a food reward. During a probe test (b) the entrance is switched to the northern arm and food is removed. A left turn in the direction of the food reward during training indicates an A-O driven ‘place strategy’, a right turn an inflexible ‘response strategy’ (re-drawn from Yin and Knowlton, 2006)Table 1 A summary of cognitive and behavioural tests to profile the equine endophenotype from an applied perspective.TestDescriptionPsychological metricPreviously tested in horsesApplication to equine training and welfareProgressive ratioThe number of correct operant responses for a reward is increased progressively. The point at which the animal stops responding is referred to as the break point ADDIN EN.CITE <EndNote><Cite><Author>Roberts</Author><Year>1989</Year><RecNum>6002</RecNum><IDText>Self-administration of cocaine on a progressive ratio schedule in rats-dose response relationship and effect of haloperidol pretreatment.</IDText><DisplayText>(Roberts et al., 1989)</DisplayText><record><rec-number>6002</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820493">6002</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Roberts, D. C. S.</author><author>Loh, E. A.</author><author>Vickers, G.</author></authors></contributors><titles><title>Self-administration of cocaine on a progressive ratio schedule in rats-dose response relationship and effect of haloperidol pretreatment.</title><secondary-title>Psychopharmacology</secondary-title></titles><periodical><full-title>Psychopharmacology</full-title><abbr-1>Psychopharmacology</abbr-1><abbr-2>Psychopharmacology</abbr-2></periodical><pages>535-538</pages><volume>97</volume><number>4</number><dates><year>1989</year><pub-dates><date>1989</date></pub-dates></dates><isbn>0033-3158</isbn><accession-num>WOS:A1989T906300019</accession-num><urls><related-urls><url><Go to WoS>://WOS:A1989T906300019</url></related-urls></urls><electronic-resource-num>10.1007/bf00439560</electronic-resource-num></record></Cite></EndNote>(Roberts et al., 1989)Measures motivation and apathyYes ADDIN EN.CITE <EndNote><Cite><Author>Houpt</Author><Year>2012</Year><RecNum>5990</RecNum><IDText>Motivation for cribbing by horses</IDText><DisplayText>(Houpt, 2012)</DisplayText><record><rec-number>5990</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5990</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Houpt, K. A.</author></authors></contributors><titles><title>Motivation for cribbing by horses</title><secondary-title>Animal Welfare</secondary-title></titles><periodical><full-title>Animal Welfare</full-title><abbr-1>Anim. Welfare</abbr-1><abbr-2>Anim Welfare</abbr-2></periodical><pages>1-7</pages><volume>21</volume><number>1</number><dates><year>2012</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0962-7286</isbn><accession-num>WOS:000299905700001</accession-num><urls><related-urls><url><Go to ISI>://WOS:000299905700001</url></related-urls></urls></record></Cite></EndNote>(Houpt, 2012)Potential marker of hyper-motivation and stereotypy predisposition?Marker of reward sensitivityExtra-intra-dimensional shift/ discrimination-reversalTwo-choice discrimination and reversal of visual object based on different rules e.g. shape and colour ADDIN EN.CITE <EndNote><Cite><Author>Dias</Author><Year>1996</Year><RecNum>3209</RecNum><IDText>Dissociation in prefrontal cortex of affective and attentional shifts</IDText><DisplayText>(Dias et al., 1996)</DisplayText><record><rec-number>3209</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820234">3209</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dias, R.</author><author>Robbins, T. W.</author><author>Roberts, A. C.</author></authors></contributors><auth-address>Department of Experimental Psychology, University of Cambridge, UK.</auth-address><titles><title>Dissociation in prefrontal cortex of affective and attentional shifts</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title><abbr-1>Nature</abbr-1><abbr-2>Nature</abbr-2></periodical><pages>69-72</pages><volume>380</volume><number>6569</number><edition>1996/03/07</edition><keywords><keyword>Affect/*physiology</keyword><keyword>Animals</keyword><keyword>Attention/*physiology</keyword><keyword>*Brain Mapping</keyword><keyword>Callithrix</keyword><keyword>Cognition/*physiology</keyword><keyword>Photomicrography</keyword><keyword>Prefrontal Cortex/*physiology</keyword><keyword>Quinolinic Acid/administration & dosage</keyword><keyword>Retention (Psychology)/physiology</keyword><keyword>Visual Perception/*physiology</keyword></keywords><dates><year>1996</year><pub-dates><date>Mar 7</date></pub-dates></dates><isbn>0028-0836 (Print)</isbn><accession-num>8598908</accession-num><urls><related-urls><url>;(Dias et al., 1996)Measures flexibility of learning and attentionYes PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJ0aW48L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (Sappington et al., 1997; Martin et al., 2006)Marker for flexible learning critical for complex tasks and successive approximationExtinction Learning Animal is taught an operant response for food reward. This is followed by removal of the positive reinforcer. Latency / trials to response cessation is recorded. Measures perseverance / habitual responding Yes ADDIN EN.CITE <EndNote><Cite><Author>Hemmings</Author><Year>2007</Year><RecNum>54</RecNum><IDText>Perseverative responding and the aetiology of equine oral stereotypy</IDText><DisplayText>(Hemmings et al., 2007)</DisplayText><record><rec-number>54</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819837">54</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hemmings, A.</author><author>McBride, S. D.</author><author>Hale, C. E.</author></authors></contributors><titles><title>Perseverative responding and the aetiology of equine oral stereotypy</title><secondary-title>Applied Animal Behaviour Science</secondary-title></titles><periodical><full-title>Applied Animal Behaviour Science</full-title><abbr-1>Appl. Anim. Behav. Sci.</abbr-1><abbr-2>Appl Anim Behav Sci</abbr-2></periodical><pages>143-150</pages><volume>104</volume><number>1-2</number><dates><year>2007</year></dates><isbn>0168-1591</isbn><accession-num>WOS:000245800300013</accession-num><urls></urls><electronic-resource-num>10.1016/j.applanim.2006.04.031</electronic-resource-num></record></Cite></EndNote>(Hemmings et al., 2007) Identifies animals which may be prone to habitual response patterns during training 5 choice serial reaction time testOperant movement towards one of five briefly (e.g. 0.5s ) lighted areas with errors of movement recorded during the inter-trial interval (e.g. 5s) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XZWVkPC9BdXRob3I+PFllYXI+MTk5OTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (Weed et al., 1999)Measures attention and impulsivityNoMarker for impulsivity and poor attention which will affect training rate. May also be a potential marker for stereotypy predisposition.Concurrent schedules/concurrent chain schedulesChoosing between two concurrently presented stimuli, each of which is associated with a different reward value ADDIN EN.CITE <EndNote><Cite><Author>Grace</Author><Year>1998</Year><RecNum>5991</RecNum><IDText>Effects of unsignaled delay of reinforcement on preference and resistance to change</IDText><DisplayText>(Grace et al., 1998)</DisplayText><record><rec-number>5991</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5991</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Grace, R. C.</author><author>Schwendiman, J. W.</author><author>Nevin, J. A.</author></authors></contributors><titles><title>Effects of unsignaled delay of reinforcement on preference and resistance to change</title><secondary-title>Journal of the Experimental Analysis of Behavior</secondary-title></titles><periodical><full-title>Journal of the Experimental Analysis of Behavior</full-title><abbr-1>J. Exp. Anal. Behav.</abbr-1><abbr-2>J Exp Anal Behav</abbr-2></periodical><pages>247-261</pages><volume>69</volume><number>3</number><dates><year>1998</year><pub-dates><date>May</date></pub-dates></dates><isbn>0022-5002</isbn><accession-num>WOS:000073526300002</accession-num><urls><related-urls><url><Go to ISI>://WOS:000073526300002</url></related-urls></urls><electronic-resource-num>10.1901/jeab.1998.69-247</electronic-resource-num></record></Cite></EndNote>(Grace et al., 1998)Measures motivation and impulsivity.Yes, ADDIN EN.CITE <EndNote><Cite><Author>Parker</Author><Year>2008</Year><RecNum>53</RecNum><IDText>Impaired instrumental choice in crib-biting horses (Equus caballus)</IDText><DisplayText>(Parker et al., 2008)</DisplayText><record><rec-number>53</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819837">53</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parker, M.</author><author>Redhead, E. S.</author><author>Goodwin, D.</author><author>McBride, S. D.</author></authors></contributors><titles><title>Impaired instrumental choice in crib-biting horses (Equus caballus)</title><secondary-title>Behavioural Brain Research</secondary-title></titles><periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></periodical><pages>137-140</pages><volume>191</volume><number>1</number><dates><year>2008</year></dates><isbn>0166-4328</isbn><accession-num>WOS:000256786700019</accession-num><urls></urls><electronic-resource-num>10.1016/j.bbr.2008.03.009</electronic-resource-num></record></Cite></EndNote>(Parker et al., 2008) Potential marker for impulsive choice/lack of self-control which will affect training rate. May also be a potential marker for stereotypyPlace-response learningAnimal is trained continuously to approach a goal in the same arm of a T-maze. In a probe trial, the animal enters the maze from the opposite arm to training ADDIN EN.CITE <EndNote><Cite><Author>Tolman</Author><Year>1949</Year><RecNum>5992</RecNum><IDText>Studies in spatial learning; place and response learning under different degrees of motivation</IDText><DisplayText>(Tolman and Gleitman, 1949)</DisplayText><record><rec-number>5992</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5992</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tolman, E. C.</author><author>Gleitman, H.</author></authors></contributors><titles><title>Studies in spatial learning; place and response learning under different degrees of motivation</title><secondary-title>Journal of experimental psychology</secondary-title></titles><periodical><full-title>Journal of Experimental Psychology</full-title><abbr-1>J. Exp. Psychol.</abbr-1><abbr-2>J Exp Psychol</abbr-2></periodical><pages>653-9</pages><volume>39</volume><number>5</number><dates><year>1949</year><pub-dates><date>1949-Oct</date></pub-dates></dates><isbn>0022-1015</isbn><accession-num>MEDLINE:15391108</accession-num><urls><related-urls><url><Go to ISI>://MEDLINE:15391108</url></related-urls></urls><electronic-resource-num>10.1037/h0059317</electronic-resource-num></record></Cite></EndNote>(Tolman and Gleitman, 1949)Measures habit formationYes ADDIN EN.CITE <EndNote><Cite><Author>Parker</Author><Year>2009</Year><RecNum>1613</RecNum><IDText>Differential place and response learning in horses displaying an oral stereotypy</IDText><DisplayText>(Parker et al., 2009)</DisplayText><record><rec-number>1613</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819943">1613</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parker, Matthew</author><author>McBride, Sebastian D.</author><author>Redhead, Edward S.</author><author>Goodwin, Deborah</author></authors></contributors><titles><title>Differential place and response learning in horses displaying an oral stereotypy</title><secondary-title>Behavioural Brain Research</secondary-title></titles><periodical><full-title>Behavioural Brain Research</full-title><abbr-1>Behav. Brain Res.</abbr-1><abbr-2>Behav Brain Res</abbr-2></periodical><pages>100-105</pages><volume>200</volume><number>1</number><keywords><keyword>Horse</keyword><keyword>Stereotypy</keyword><keyword>Habit</keyword><keyword>Place/response</keyword></keywords><dates><year>2009</year></dates><isbn>0166-4328</isbn><urls><related-urls><url>;(Parker et al., 2009)Potential marker for stereotypy. Potential marker for behavioural inflexibility and habit formation which will have implications on learning abilityPre-pulse inhibitionExposure to a weak ‘pre’pulse attenuates the reaction to a stronger stimulus (pulse)This is a measure of the startle reflex, and is known to be disrupted in patients with neurological conditions and some neuropsychiatric disordersNoPotential marker for poor impulse control and poor executive function. This will have implications for learning abilityJudgement biasAnimals are trained on two conditioned stimuli (positive and negative) and then presented with an ambiguous conditioned stimulus ADDIN EN.CITE <EndNote><Cite><Author>Harding</Author><Year>2004</Year><RecNum>1537</RecNum><IDText>Animal behavior - Cognitive bias and affective state</IDText><DisplayText>(Harding et al., 2004)</DisplayText><record><rec-number>1537</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453819934">1537</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Harding, E. J.</author><author>Paul, E. S.</author><author>Mendl, M.</author></authors></contributors><titles><title>Animal behavior - Cognitive bias and affective state</title><secondary-title>Nature</secondary-title><short-title>Animal behavior - Cognitive bias and affective state</short-title></titles><periodical><full-title>Nature</full-title><abbr-1>Nature</abbr-1><abbr-2>Nature</abbr-2></periodical><pages>312-312</pages><volume>427</volume><number>6972</number><dates><year>2004</year><pub-dates><date>Jan 22</date></pub-dates></dates><accession-num>ISI:000188266200030</accession-num><urls><related-urls><url><Go to ISI>://000188266200030</url></related-urls></urls></record></Cite></EndNote>(Harding et al., 2004)(Harding et al., 2004) The response to the ambiguous conditioned stimulus is potential measure of optimism/pessimism and an inferred measure of emotional state.Yes ADDIN EN.CITE <EndNote><Cite><Author>Freymond</Author><Year>2014</Year><RecNum>5993</RecNum><IDText>Behaviour of horses in a judgment bias test associated with positive or negative reinforcement</IDText><DisplayText>(Freymond et al., 2014)</DisplayText><record><rec-number>5993</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5993</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freymond, Sabrina Briefer</author><author>Briefer, Elodie F.</author><author>Zollinger, Anja</author><author>Gindrat-von Allmen, Yveline</author><author>Wyss, Christa</author><author>Bachmann, Iris</author></authors></contributors><titles><title>Behaviour of horses in a judgment bias test associated with positive or negative reinforcement</title><secondary-title>Applied Animal Behaviour Science</secondary-title></titles><periodical><full-title>Applied Animal Behaviour Science</full-title><abbr-1>Appl. Anim. Behav. Sci.</abbr-1><abbr-2>Appl Anim Behav Sci</abbr-2></periodical><pages>34-45</pages><volume>158</volume><dates><year>2014</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0168-1591</isbn><accession-num>WOS:000341480200005</accession-num><urls><related-urls><url><Go to ISI>://WOS:000341480200005</url></related-urls></urls><electronic-resource-num>10.1016/j.applanim.2014.06.006</electronic-resource-num></record></Cite></EndNote>(Freymond et al., 2014)A potential welfare indicator of training techniques and husbandry environments.May also be a useful probe for ‘mood’ in relation to performance ADDIN EN.CITE <EndNote><Cite><Author>McBride</Author><Year>2012</Year><RecNum>5407</RecNum><IDText>Psychological factors affecting equine performance</IDText><DisplayText>(McBride and Mills, 2012)</DisplayText><record><rec-number>5407</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820438">5407</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McBride, Sebastian D.</author><author>Mills, Daniel S.</author></authors></contributors><titles><title>Psychological factors affecting equine performance</title><secondary-title>Bmc Veterinary Research</secondary-title></titles><periodical><full-title>BMC Veterinary Research</full-title><abbr-1>BMC Vet. Res.</abbr-1><abbr-2>BMC Vet Res</abbr-2></periodical><volume>8</volume><dates><year>2012</year><pub-dates><date>Sep 27</date></pub-dates></dates><isbn>1746-6148</isbn><accession-num>WOS:000312669100001</accession-num><urls><related-urls><url><Go to ISI>://WOS:000312669100001</url></related-urls></urls><custom7>180</custom7><electronic-resource-num>10.1186/1746-6148-8-180</electronic-resource-num></record></Cite></EndNote>(McBride and Mills, 2012)Spontaneous blink rateRate of bilateral brief repetitive eye closures that occur continuously and in the absence of obvious external stimuli, and is not affected by external stimuli such as light, heat or humidity. ADDIN EN.CITE <EndNote><Cite><Author>Karson</Author><Year>1983</Year><RecNum>2</RecNum><IDText>Spontaneous Eye-Blink Rates and Dopaminergic Systems</IDText><DisplayText>(Karson, 1983)</DisplayText><record><rec-number>2</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">2</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Karson, C.N.</author></authors></contributors><titles><title>Spontaneous Eye-Blink Rates and Dopaminergic Systems</title><secondary-title>Brain</secondary-title></titles><pages>643-653</pages><volume>106</volume><dates><year>1983</year></dates><urls></urls></record></Cite></EndNote>(Karson, 1983).Habit formation and impulsivityYes ADDIN EN.CITE <EndNote><Cite><Author>Roberts</Author><Year>2015</Year><RecNum>6732</RecNum><IDText>Cognitive differences in horses performing locomotor versus oral stereotypic behaviour</IDText><DisplayText>(Roberts et al., 2015)</DisplayText><record><rec-number>6732</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1455787209">6732</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Roberts, Kirsty</author><author>Hemmings, Andrew</author><author>Moore-Colyer, Meriel</author><author>Hale, Catherine</author></authors></contributors><titles><title>Cognitive differences in horses performing locomotor versus oral stereotypic behaviour</title><secondary-title>Applied Animal Behaviour Science</secondary-title></titles><periodical><full-title>Applied Animal Behaviour Science</full-title><abbr-1>Appl. Anim. Behav. Sci.</abbr-1><abbr-2>Appl Anim Behav Sci</abbr-2></periodical><pages>37-44</pages><volume>168</volume><dates><year>2015</year></dates><publisher>Elsevier</publisher><isbn>0168-1591</isbn><urls><related-urls><url>;(Roberts et al., 2015)As an indirect measure of dopaminergic tone, this may be a useful marker for stereotypy predisposition, accelerated habit formation and/or impulsivity. Behavioural switching frequencyUsing a defined species-specific ethogram, this test monitors the rate of switching from one behaviour to another ADDIN EN.CITE <EndNote><Cite><Author>Garner</Author><Year>2006</Year><RecNum>7</RecNum><IDText>Perseveration and stereotypy - Systems level insights from clinical psychology</IDText><DisplayText>(Garner, 2006)</DisplayText><record><rec-number>7</rec-number><foreign-keys><key app="EN" db-id="ef9sw52rdxrs2lesz5dvtee12z9ersss229t" timestamp="1457018485">7</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Garner, J. P.</author></authors><secondary-authors><author>Mason, G.</author><author>Rushen, J.</author></secondary-authors></contributors><titles><title>Perseveration and stereotypy - Systems level insights from clinical psychology</title><secondary-title>Stereotypic animal behaviour - Fundamentals and applications to welfare</secondary-title></titles><edition>Second</edition><dates><year>2006</year></dates><publisher>Cabi</publisher><urls></urls></record></Cite></EndNote>(Garner, 2006)Habit formation and impulsivityYes ADDIN EN.CITE <EndNote><Cite><Author>Roberts</Author><Year>2015</Year><RecNum>6732</RecNum><IDText>Cognitive differences in horses performing locomotor versus oral stereotypic behaviour</IDText><DisplayText>(Roberts et al., 2015)</DisplayText><record><rec-number>6732</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1455787209">6732</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Roberts, Kirsty</author><author>Hemmings, Andrew</author><author>Moore-Colyer, Meriel</author><author>Hale, Catherine</author></authors></contributors><titles><title>Cognitive differences in horses performing locomotor versus oral stereotypic behaviour</title><secondary-title>Applied Animal Behaviour Science</secondary-title></titles><periodical><full-title>Applied Animal Behaviour Science</full-title><abbr-1>Appl. Anim. Behav. Sci.</abbr-1><abbr-2>Appl Anim Behav Sci</abbr-2></periodical><pages>37-44</pages><volume>168</volume><dates><year>2015</year></dates><publisher>Elsevier</publisher><isbn>0168-1591</isbn><urls><related-urls><url>;(Roberts et al., 2015)As an indirect measure of dopaminergic tone, this may be a useful marker for stereotypy predisposition, accelerated habit formation and/or impulsivity. Pavlovian Instrumental transferA classically conditioned association is shaped to become contingent upon an operant response.Rate of transfer from autonomic to voluntary mediation of behavioural output Yes ADDIN EN.CITE <EndNote><Cite><Author>Lansade</Author><Year>2013</Year><RecNum>5994</RecNum><IDText>Dimensions of Temperament Modulate Cue-Controlled Behavior: A Study on Pavlovian to Instrumental Transfer in Horses (Equus Caballus)</IDText><DisplayText>(Lansade et al., 2013)</DisplayText><record><rec-number>5994</rec-number><foreign-keys><key app="EN" db-id="ewef0fpd9rsxzke9p9w5w2xt5zv0fefa2e9v" timestamp="1453820486">5994</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lansade, Lea</author><author>Coutureau, Etienne</author><author>Marchand, Alain</author><author>Baranger, Gersende</author><author>Valenchon, Mathilde</author><author>Calandreau, Ludovic</author></authors></contributors><titles><title>Dimensions of Temperament Modulate Cue-Controlled Behavior: A Study on Pavlovian to Instrumental Transfer in Horses (Equus Caballus)</title><secondary-title>Plos One</secondary-title></titles><periodical><full-title>PloS One</full-title><abbr-1>PLoS One</abbr-1><abbr-2>PLoS One</abbr-2></periodical><volume>8</volume><number>6</number><dates><year>2013</year><pub-dates><date>Jun 14</date></pub-dates></dates><isbn>1932-6203</isbn><accession-num>WOS:000320363300003</accession-num><urls><related-urls><url><Go to ISI>://WOS:000320363300003</url></related-urls></urls><custom7>e64853</custom7><electronic-resource-num>10.1371/journal.pone.0064853</electronic-resource-num></record></Cite></EndNote>(Lansade et al., 2013)Relevance to learning mechanisms underlying secondary reinforcement (e.g. clicker training) Figure 1Figure 2Figure 3Figure 4 ................
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