Human Higher Biology



NATIONAL QUALIFICATIONS CURRICULUM SUPPORT

Human Biology

Unit 3: Neurobiology and

Communication

A Case Study into Experience-

Driven Plasticity in the Brain

Student’s Notes

[HIGHER]

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Acknowledgement

Learning and Teaching Scotland gratefully acknowledges this contribution to the National Qualifications support programme for Human Biology.

The publisher gratefully acknowledges permission to use the following sources: Figure 1, living conditions in different experimental groups from Neural consequences of environmental enrichment, by Vann Pragg, Kempermann and Gage, December 2000, Vol 1, p.192, Nature publishing group , reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience, 191-198 (December 2000) © 2000 ; Figure a and e from More Hippocampal Neurons in Adult mice living in an enriched environment by Kempermann, Kuhn and Gage from Nature neuroscience, Vol 2 No 3, March 199 , reprinted by permission from Macmillan Publishers Ltd: Nature, Nature 386, 493-495 (3 April 1997) © 1997 ; Figure b The enhancement of visual-cortex plasticity from Enrich the Environment to empower the brain by Sale Berardi and Maffei from trends in neurosciences Vol 32 no 4, page 23 (09)00026-5, reprinted from Trends in Neurosciences, Volume 32, Issue 4, Sale Berardi and Maffei, Enrich the Environment to Empower the Brain, p 237, 2008 with permission from Elsevier; Diagram Watermaze: latency (s) from Experience Induced Neurogenesis in the senescent dentate gyrus by Kempermann, Kuhn and Gage, 3210 J Neurosci, May 1 1998 18(9):3206-3212, Society for Neuroscience p 3210, 1998, reprinted from Experience Induced Neurogenesis in the senescent dentate gyrus by Kempermann, Kuhn and Gage, Society for Neuroscience; Diagram a ocular dominance from critical period plasticity in local circuits by Takao Hensch, Nature Reviews/Neuroscience, Vol 6, p 978, November 2005 , reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience 6, 877-888 (November 2005) © 2005

© Learning and Teaching Scotland 2011

This resource may be reproduced in whole or in part for educational purposes by educational establishments in Scotland provided that no profit accrues at any stage.

Contents

Introduction 4

What is environmental enrichment and how does it shape the brain? 5

Activity 1: Interpreting experimental data relating to environmental enrichment 5

Sensory deprivation and brain plasticity 8

Activity 2: Interpreting experimental data relating to sensory

deprivation 9

The concept of critical period in developmental plasticity 11

Introduction

This case study aims to reinforce the concept of neuronal plasticity by discussing environmental enrichment and sensory deprivation as experimental strategies.

Activities will be based on interpreting basic scientific data from key experiments in the field.

Background

Neuronal plasticity is a central theme in neurobiology and refers to changes in the brain as a result of environmental experience. At a cellular level, this is called synaptic plasticity and is the ability of nerve cell connections (synapses) to change in strength in response to their stimulation or inhibition.

Synaptic plasticity is an important concept underlying the biological processes involved in learning and memory.

In 1949 Donald Hebb proposed a mechanism for synaptic plasticity in his book The Organisation of Behaviour.

He stated that an increase in the strength of a synapse arises from the pre-synaptic cell repeatedly and persistently stimulating the post-synaptic cell.

In other words ‘cells that fire together wire together’.

Hebb based his theory on a simple observation. He noticed that rats he took home as pets showed improvements in problem-solving tasks compared to litter mates kept in laboratory cages.

He suggested that a stimulating environment enhanced the strength of synaptic connections in the pet rats compared to caged animals. Hebb was unwittingly the first to introduce environmental enrichment as an experimental concept to measure synaptic plasticity.

What is environmental enrichment and how does it shape the brain?

In experimental terms, an enriched environment is a combination of complex inanimate social stimulation. Enriched rodents are kept in larger cages and in larger groups, with the opportunity for more varied and complex interaction. Animals are given tunnels, nesting material, running wheels and toys, and food and water locations are often changed on a regular basis. These rodents are experiencing greater environmental stimulation compared to rodents housed in standard wire cages.

Environmental enrichment leads to anatomical, behavioural and molecular changes in the brain. Enriched rodents have bigger and heavier brains. Neurons are larger, with a greater spread of dendrites. Synaptic connections are larger in size and number. Enriched rodents perform better in learning and memory tasks. Gene expression is also altered in response to environmental enrichment.

Activity 1: Interpreting experimental data relating to environmental enrichment

Experimental task

Examine the effect of environmental enrichment on the structure and function of the hippocampus (the part of the mid-brain involved in learning and memory) in adult mice.

Materials and methods

18-month-old animals were split into two groups, enriched and control.

Enriched mice were housed in a large cage (86 × 76 cm) and enrichment consisted of social interaction (13 mice per cage) and stimulation of exploratory behaviour and physical activity with objects such as toys, tunnels and a running wheel.

Control mice were housed in a standard sized cage (30 × 18 cm) with limited social interaction (three mice per cage) and environmental stimulation.

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Enriched vs control environments

Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews: Neuroscience, 191–198 (December 2000) © 2000

Following 40 days in their respective environments, half the mice in each group were injected with BrdU (a marker of cell division). A day later, brains were removed. Sections of the hippocampus were treated with staining chemicals to detect the presence of BrdU.

The remaining mice in each group were tested on their ability to learn the location of a submerged platform in a pool of water. The time taken (latency) to find the platform was automatically recoded using a video tracking device. Mice were tested everyday for 10 days, each test lasting for a maximum of 60 seconds or until the mouse had found the platform.

Results and conclusion

Interpret the results of the experiment shown below. For Figure 1, you might consider quantifying the data by counting the number of black dots (ie BrdU staining) for enriched and control mice, and plotting it on a graph.

Figure 1

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Hippocampal sections of enriched and control mice 1 day after BrdU exposure

Reprinted by permission from Macmillan Publishers Ltd: Nature, Nature 386, 493-495 (3 April 1997) © 1997

Figure 2

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Latency to locate the submerged platform over 10 days for enriched and control mice

Reprinted from Experience Induced Neurogenesis in the senescent dentate gyrus by Kempermann, Kuhn and Gage, Society for Neuroscience.

Sensory deprivation and brain plasticity

Just as environmental enrichment can alter the structure and function of the brain, so too can exposure to deprived environments. Since the early 1960s this concept has been extensively studied using the development of vision as a model system.

Normal vision relies on early sensory exposure to light, activating cells in the visual part of the brain and shaping synapses to generate highly organised patterns of connections.

Visual processing occurs at the back of the brain in the primary visual cortex. Each half of the brain has a visual cortex, and under normal visual development the left side processes sensory information covering the right field of vision and the right side processes information covering the left field of vision. A region of the visual cortex called the binocular zone also receives sensory information from both eyes.

Early experiments investigating visual deprivation were performed on kittens using an experimental technique called monocular deprivation. This involves the closure of one eye through eyelid suture early in development.

Occluding one eye through monocular deprivation severely disrupts plasticity during visual development. Visual neurons become disproportionally targeted towards the open eye, increasing in number and complexity at the expense of the closed eye.

The ability of the brain to prefer visual input from the open eye over the closed eye is called ocular dominance. Ocular dominance can be observed on a much less severe scale using our everyday vision. You probably have one eye that can read letter boards in the opticians better than the other. For most people, the right eye has ocular dominance over the left eye.

Activity 2: Interpreting experimental data relating to sensory deprivation

Experimental task

Examine the effect of monocular deprivation on the ocular dominance of visual cortex neurons in the mouse.

Materials and methods

An adolescent mouse (28 days old) was subject to monocular deprivation for a period of 4 days. Under anaesthesia, the left eyelid of the animal was sewn closed. Following surgery, the mouse was returned to its home cage and checked daily. After 4 days, sutures were removed.

To assess the responsiveness of neurons to monocular deprivation electrical activity was recorded from cells within the visual cortex. Specialised electrodes were inserted into the brain to allow recordings from single cells.

During recordings, a stimulus of light was presented to each eye alternately and the strength of the response measured for each cell. Twenty-five cells originating from the right side of the visual cortex were recorded from in total.

Each cell was assigned an ocular dominance score ranging from 1 to 7.

A score of 1 was given to a cell that responded exclusively to stimuli presented to the eye opposite to the side of the brain the recoding was made from. A score of 7 was given to a cell that responded exclusively to stimuli presented to the eye on the same side of the brain the recoding was taken from.

Cells responding equally to stimuli presented to both eyes were assigned a score of 4. Scores of 2 and 3 were assigned to a cell if it responded better to stimuli presented to the eye opposite to the site of recording. Similarly, a cell received a score of 5 or 6 if it responded better to stimuli presented to eye on the same side of the brain to the site of recording.

Ocular dominance scores:

1 – Response exclusively opposite

2 – Mostly opposite response

3 – Opposite eye still dominating response, but less so

4 – Equal response from both eyes

5 – Eye on same side as recording still dominating response, but less so

6 – Mostly same side response

7 – Response exclusively same side

The activity of cells from a normal, non-deprived mouse of the same age were recorded from in the same way, and the percentage of cells representing each ocular dominance score compared.

Result and conclusions

Interpret the results of the experiment as shown below. Consider the following points in your answer:

• How are cells responding in the non-deprived mouse?

• What happens to this response after 4 days of deprivation?

• How is this difference represented graphically?

• What is happening to ocular dominance scores?

• How does this compare to normal visual development?

Figure 1

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Neural responsiveness in the visual cortex of non-deprived (left) and deprived (right) mice

Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews: Neuroscience 6, 877-888 (November 2005) © 2005

The concept of critical period in developmental plasticity

In contrast to adolescent mice, monocular manipulation in adult mice is totally ineffective. If a mouse experiences deprivation at 3 months the shift in ocular dominance that arises with deprivation at 28 days does not occur.

This is because a critical period of plasticity exists during early development whereby the brain is more sensitive to certain environmental stimuli. During this time, neural connections are constantly being shaped in response to sensory experience.

If an appropriate stimulus is not received during the critical period it may be difficult to develop a particular brain function later in life. For example, monocular deprivation in mice results in permanent visual impairment in the adult if left untreated. However, if the effect is removed before the end of the critical period a full recovery is possible.

The length of the critical period is proportionally correlated with lifespan – the longer the lifespan, the longer the critical period. In humans the critical period lasts for years compared to only a few weeks in mice.

Although the visual system is the most widely studied, critical periods have also been shown to exist for auditory response and, in humans, language development.

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Reprinted from Trends in Neuroscience, Volume 32, Issue 4, Sale Berardi and Maffei, Enrich the Environment to Empower the Brain, p237, 2008 with permission from Elsevier

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