NATIONAL QUALIFICATIONS CURRICULUM SUPPORT
Human Biology
Unit 3: Neurobiology and
Communication
A Case Study into ExperienceDriven 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 http://www.nature.com/nrn/journal/v1/n3/full/nrn1200_191a.html, reprinted
by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience, 191-198
(December 2000) © 2000 http://www.nature.com/nrn/index.html; 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
http://www.nature.com/nature/journal/v386/n6624/pdf/386493a0.pdf, reprinted by permission
from Macmillan Publishers Ltd: Nature, Nature 386, 493-495 (3 April 1997) © 1997
http://www.nature.com/nature/index.html; 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
http://www.cell.com/trends/neurosciences/abstract/S0166-2236(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
http://www.nature.com/nrn/journal/v6/n11/full/nrn1787.html, reprinted by permission from
Macmillan Publishers Ltd: Nature Reviews Neuroscience 6, 877-888 (November 2005) © 2005
http://www.nature.com/nrn/index.html
© 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.
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A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
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
A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
11
3
STUDENT’S NOTES
Introduction
This case study aims to reinforce the concept o f 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.
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A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
STUDENT’S NOTES
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 wheel s 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 an d 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.
A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
5
STUDENT’S NOTES
Control mice were housed in a standard sized cage (30 × 18 cm) with limited
social interaction (three mice per cage) and environmental stimulation.
Enriched vs control environments
Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews:
Neuroscience, 191–198 (December 2000) © 2000
http://www.nature.com/nrn/index.html
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 tr eated 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 Fi gure 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.
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A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
STUDENT’S NOTES
Figure 1
Hippocampal sections of enriched and control mice 1 day after BrdU
exposure
Reprinted by permission from Macmillan Publishers Ltd: Nature, Nature 386, 493495 (3 April 1997) © 1997 http://www.nature.com/nature/index.html
Figure 2
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.
A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
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STUDENT’S NOTES
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 i n 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.
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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A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
STUDENT’S NOTES
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. Special ised
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
2
3
4
5
–
–
–
–
–
Response exclusively opposite
Mostly opposite response
Opposite eye still dominating response, but less so
Equal response from both eyes
Eye on same side as recording still dominating response, but less so
A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
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STUDENT’S NOTES
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
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
http://www.nature.com/nrn/index.html
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A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
STUDENT’S NOTES
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 do es 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. I n 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.
A CASE STUDY INTO EXPERIENCE DRIVEN PLASTICITY IN THE BRAIN (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
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