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Tourette Syndrome is an inherited neurological condition. People with Tourette Syndrome experience quirky tics that are generally vocal and motor (movement). The underlying cause of Tourette Syndrome is thought to be related to neurotransmitters. One of the ways this has been shown is by examining people who use medications that promote more dopamine (a neurotransmitter) function. These people find that their tics worsen on dopamine-helping medications. Feel free to go to to learn more about Tourette Syndrome. Now that you understand the brain, and the cells of the brain, it is important to turn to how cells of the brain communicate with each other. Actually, neurons can communicate with other neurons or muscles through chemical synapses and neurons outside the brain also use synapses. A synapse consists of the two cells that are communicating and the space between them. The neuron itself uses electrical signaling (review “the membrane” if this is unclear). But once the electrical message reaches the neuron ends, the synaptic bulbs, that message gets converted into a chemical form. MANY of the drugs we will discuss in this course operate at the level of the synapse. They can either aide in neurotransmission between neurons or inhibit this communication. ObjectivesAfter successfully completing this lesson you will be able to:to understand how two electrical cells communicate with each otherto understand what a neurotransmitter is, and how it is: packaged, released, recognized, metabolized, and recycledto differentiate between excitatory synaptic events and inhibitory onesto put synapse formation and loss in the context of learningBefore you begin! PretestAt rest, 169862510414000Lesson: The SynapseGuiding QuestionsHow do neurons know to have an action potential?Once they have an action potential, how do they communicate to other cells?What is the form of the message sent from a neuron?How does that signal get regulated?In what ways can drugs influence synapse function?How are positive and negative signals conveyed to a neuron??Key TermsNeurotransmitterExocytosisVesicleReceptorRecycling TransporterMonoamineMonoamine oxidaseAcetylcholineSerotoninDopamineNorepinephrineGABAGlutamateActivity One: Web Site ReviewStart this lesson at NeuroScience for Kids page on synapses - Guiding questions as you view this page are:What parts of a neuron are involved in a synapse?Synapse can form between two cells of what type(s)?How are neurotransmitters stored, and in what part of a neuron?How are neurotransmitters released?Next view the animation at Guiding questions for this video include: Why do we need neurotransmitters?What are four main things that happen to a neurotransmitter in a synapse?What events lead to the release of neurotransmitter?What does binding between neurotransmitter and postsynaptic cell accomplish?Next view the animation at Guiding questions for this video include:What do pre- and post-synaptic terms refer to?What causes neurotransmitter to be released? How is neurotransmitter released?What happens to neurotransmitter after it is released?Next view the animation at Guiding questions for this video include: Why do we need neurotransmitters?What are four main things that happen to a neurotransmitter in a synapse?What events lead to the release of neurotransmitter?What does binding between neurotransmitter and postsynaptic cell accomplish?Activity Two: The Presynaptic Neuron214884010668000The diagram to the right represented a neuron in the previous lesson. If we imagine this to be the pre-synaptic neuron, which part will be involved in communicating to the post-synaptic neuron? The synaptic bulbs on the rightTaking a closer look at this presynaptic neuron (image citation – Audesirk and Audesirk – copyrighted), and in particular at the synaptic bulb, you’ll see a couple of noteworthy features. 402717058420The axon widens at these ends, and within this specialized ending are vesicles. These spherical compartments are surrounded by internal membranes. Their importance is that they contain neurotransmitters. Neurotransmitters are chemicals that a neuron can release and which will convey information to a nearby cell. Therefore this presynaptic cell’s main job (at the synapse) is to release neurotransmitter.An action potential that reaches the synaptic bulb causes vesicles to migrate to the membrane at the end of the bulb. When membranes meet, the similarity in their composition causes them to fuse to each other. When a vesicle membrane and cell membrane fuse, the insides (below – image citation ) of the vesicle are released all together in a process called exocytosis. (Exo – out of, cyto – cell, sis - process). TEST OF CONTENTUsing the clues in this activity, what does endocytosis mean? Process of taking something inside the cell. History Side Bar JENActivity Three: NeurotransmittersIf you return to the neurotransmitter page at Neuroscience for Kids, you’ll see there are fairly rigid criteria for defining a molecule as a neurotransmitter. It’s an exclusive club. Make note of what is required to join the neurotransmitter group. Often students tell us that endorphins are neurotransmitters. Check and see why this is not entirely accurate.The neurotransmitter names necessary to know in this class are represented by the word SNAGGED.Serotonin, norepinephrine, acetylcholine, glutamate, GABA, epinephrine, and dopamine. 4204970452120First, look at the structures of dopamine, serotonin, epinephrine, and norepinephrine. 2298709537704128770623570Note to self - Top row – epinephrine (CHs spelled out) on left, norepinephrine on the right. Norepi has removed the methyl and added a hydroxyl. NH is not an amine, so only norepi is a monoamine. Bottom row, serotonin on left, dopamine on right.Epinephrine and norepinephrine are related as their names suggest. But only one has an NH2 group. Both dopamine and serotonin have an NH2 group. Thus norepinephrine, serotonin, and dopamine are “mono amine” neurotransmitters. This is important in that they share similar fates in the synapse as you will see soon.3169920-591185All neurotransmitters have structural and chemical properties that make them good candidates for binding to specific receptors. (image citation – ). Similarly, their chemistry determines other events that take place once the neurotransmitter is in the synapse.TEST OF CONTENTWhich criteria are necessary to call a molecule a neurotransmitter? Note all that are correct.It is a chemical produced by a neuron.It can only be found in the synapse.After release, it can be removed by degradation or recycling.It can act on a neuron to excite or inhibit it.It can act on a muscle to excite it.It travels long distances to achieve its goal.Activity Four: Neurotransmitter in the Synaptic CleftThe neurotransmitter that gets released by the pre-synaptic cell can be:diffused across synapse where it can bind to receptors on the post synaptic cellmetabolized by an enzymatic modification that renders it non-functionalrecycled into the presynaptic neuron for later use.Because the concentration of neurotransmitter inside the vesicle that is opening is higher than the concentration of that neurotransmitter in the external space, diffusion will carry the neurotransmitter across the space. By chance, some neurotransmitter molecules will bind to neurotransmitter receptors on the post synaptic cell membrane. Like any ligand-receptor interaction, the receptors on the post-synaptic membrane have a chemical complementarity to the neurotransmitter (ligand). All biological molecules have a limited “shelf life” (half life is a term we will define in Unit 2), and neurotransmitters are no exception. The neurotransmitter hanging around can be metabolized by enzymes that will break them down. So some neurotransmitter will leave the synapse due to decay. Each neurotransmitter is metabolized in a unique way thanks to specific enzyme reactions. One of the reasons we focused previously on monoamines (serotonin, dopamine, norepinephrine) is that they are all metabolized by monoamine oxidases. This will be important in our stimulants unit. Lastly, neurons, like any cell, need to be thrifty with their molecular resources. A neuron therefore has a mechanism to recycle neurotransmsitter molecules after release. To recycle specific molecules, membrane pumps are used, specifically recycling transporters. Once recycled, the neurotransmitter molecules are rebundled into vesicles where they will be ready for release in the future.To summarize, a neurotransmitter molecule will diffuse, be metabolized, and be recycled after release.TEST OF CONTENTWhich of the following diagrams shows a mono amine? Not all of these are molecules you have previously seen.Diagrams here with A,B,C, DActivity Five: The Post-synaptic Neuron4312920437515Neurotransmitter that is released into the synapse can diffuse across the space and bind to receptors on the post synaptic cell. These receptors are found on the dendrite and the cell body. In the scanning electron microscope image(image source unknown) , the center "ball" is the cell body of a post-synaptic neuron. All the little Y-shaped or T-shaped objects are synaptic bulbs that interact with this neuron. Each post-synaptic neuron is given information from as many as 15,000 presynaptic neurons! That is a lot of information to process while deciding what to do.Synapses form and others are lost daily. In the first year of life, humans double the number of synapses they have, and then as we age, some unused synapses get pruned away. Practicing your flute, for instance, is the only way to ensure that your body keeps the synapses around that are necessary to get the right finger positions for the notes you want to play. Without practice, the brain conserver resources and puts its energy into synapses you DO use (such as those you use to play video games). Every day we make choices that influence how our brains will work later. These choices are not just about whether to use drugs.Once the neurotransmitter binds to the receptor on the post synaptic neuron, it causes that receptor to become modified in shape and ultimately in function. Usually, one of two main events takes place.Event 1 - the binding of neurotransmitter changes the receptor in a way that opens a sodium channel.Event 2 - the binding of neurotransmitter changes the receptors in a way that opens a chloride channel.In both cases, the ion whose channel is now open is more concentrated outside the cell. So once the gates on the channel become open, the ion will flow into the neuron. The main difference is that sodium ions (Na+) are positively charged and are associated with initiation of an action potential. Chloride ions are negatively charged (Cl-). When chloride enters a neuron, that neuron becomes even MORE polarized or HYPERPOLARIZED. Its charge is now very negative. This pushes the resting potential of the neuron farther away from threshold. Visit the link below, and see what type of channel glutamate and GABA receptors act like. 4046220312420In the diagram we previously used to represent an action potential, the threshold is marked with an arrow. A hyperpolarized neurons electrical charge would be off the bottom of this graph, thus farther away from threshold.Thus if the receptor opens sodium gates, the neuron is more likely to have an action potential. If it opens chloride gates, it is LESS likely to have an action potential.40557455461000TEST OF CONTENTNot all animations online are equally accurate in representing science concepts. Just like the warnings you’ve heard about Wikipedia, YouTube videos are not peer reviewed for accuracy. See if you can spot the Inaccuracy at to contrast this, the events at the post synaptic end of this process are more accurately shown at . Do you see the difference (it’s NOT the music)? In the first, the neurotransmitter molecules enter the receptor rather than just bind to it (additionally, the neurotransmitter is recycled in the second video).In the glutamate vs. GABA animation you just visited, which (neither, glutamate, GABA, both) receptors act like chloride channels?Activity Six: To Fire or Not to Fire A post synaptic neuron will gather its many inputs and decide based on the balance of that information whether or not to fire. If the amount of chloride entering equals the amount of sodium entering, the neuron will not fire. If much more sodium enters that chloride, the neuron will become sufficiently positive to have an action potential.How can we predict if sodium or chloride will enter? For the most part, it depends upon the neurotransmitter that is bound.Neurotransmitters whose receptors are also sodium channels (therefore "excitatory")Neurotransmitters whose receptors are also chloride channels (therefore "inhibitory")DopamineGABAAcetylcholineNorepinephrineGlutamateSerotonin is not in this table because it's receptors can either be sodium or chloride channels.Activity Seven: Synapses and LearningIn your optional reading list you will find two articles that are science-for-non-scientist examples of writing. We will give you several of these to consider. Today, they are optional. But these articles come from a process by which an informed writer has taken the time to understand some science writing and make it accessible to the non-scientist. Before you can appreciate these re-written pieces, it might help to think about the process of taking science writing and making it more accessible.Take a peek at this abstract from a paper on learning and synapse formation. It is challenging to read primary science literature! You may need to read each sentence MANY times to understand and you might need a thesaurus at the ready as you do. Here is a glossary of the terms used that we have not covered:synaptogenesis = formation of new synapsesboutons = synaptic bulbsdendritic spine = dendritestratum radiatum = an area of the hippocampusassociative learning = learning that there is a pairing of one stimulus with another (tone and air puff)stereological = obtaining 3D information from a series of 2D imagesAssociative Learning Elicits the Formation of Multiple-Synapse Boutons (2001) Yuri Geinisman,?Robert W. Berry,?John F. Disterhoft,?John M. Power,?Eddy A. Van der Zee The formation of new synapses has been suggested to underlie learning and memory. However, previous work from this laboratory has demonstrated that hippocampus-dependent associative learning does not induce a net gain in the total number of hippocampal synapses and, hence, a net synaptogenesis. The aim of the present work was to determine whether associative learning involves a specific synaptogenesis confined to the formation of multiple-synapse boutons (MSBs) that synapse with more than one dendritic spine. We used the behavioral paradigm of trace eyeblink conditioning, which is a hippocampus-dependent form of associative learning. Conditioned rabbits were given daily 80-trial sessions to a criterion of 80% conditioned responses in a session. During each trial, the conditioned stimulus (tone) and the unconditioned stimulus (corneal airpuff) were presented with an intervening trace interval of 500 msec. Brain tissue was taken for morphological analyses 24 hr after the last session. Unbiased stereological methods were used for obtaining estimates of the total number of MSBs in the stratum radiatum of hippocampal subfield CA1. The results showed that the total number of MSBs was significantly increased in conditioned rabbits as compared with pseudoconditioned or unstimulated controls. This conditioning-induced change, which occurs without a net synaptogenesis, reflects a specific synaptogenesis resulting in MSB formation. Models of the latter process are proposed. The models postulate that it requires spine motility and may involve the relocation of existing spines from nonactivated boutons or the outgrowth of newly formed spines for specific synaptogenesis with single-synapse boutons activated by the conditioning stimulation.Did you understand this abstract? When ready, try "test of content".TEST OF CONTENTWhich result do these authors describe?that there are more synapses in the hippocampus after associative learningthat there are more synapses with multiple synaptic bulbs after associative learningthat rats do not show a NET increase in synapses after learningthat areas outside the hippocampus respond most vigorously to learningAre you on your way to understanding this type of science writing? Try making a "science news" type article about learning and synapse formation based just on this study. Your article should be about 1 page long, double spaced. We'll ask you to submit it to the forum associated with this synapse activity. Once your article is submitted, please read and comment on an article written by one of your classmates.Activity Eight: ReadingREQUIRED READINGFrom LiskaChapter called Drugs at the SynapseFrom any Introductory textbookSynapsesFrom Internet (recycling tranporter)SUPPLEMENTAL READINGFrom Internet ................
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