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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: image of
Morris water maze test from www.iop.kcl.ac.uk/departments/?locator=622&context=872 ©
Institute of Psychiatry, King's College London; 2 diagrams from p. 2860 of Visual Deprivation
Alters the Development of Cortical Multisensory Integration by William Vaughan, Barry E.
Stein and Mark T. Wallace, Brian N. Carriere, David W. Royal, Thomas J. Perrault, Stephen P.
Morrison, J., J Neurophysiology 98:2858-2867, 2007. First published 29 August 2007; doi:10.1152/jn.00587.2007 http://jn.physiology.org/content/98/5/2858.full.pdf+html © Visual Deprivation Alters the
Development of Cortical Multisensory Integration by William Vaughan, Barry E. Stein and
Mark T. Wallace, Brian N. Carriere, David W. Royal, Thomas J. Perrault, Stephen P.
Morrison, J.2007, Am Physiol Soc, used with permission
Every effort has been made to trace all the copyright holders but if any have been inadvertently overlooked, the publishers will be pleased to make the necessary arrangements at the first opportunity.
© 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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Overview
Activity 1: Alzheimer’s disease
Activity 2: An introduction to research in behavioural neuroscience
Activity 3: Memory-enhancing drugs
Activity 4: The effects of sensory deprivation on brain development
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STUDENT MATERIALS
This case study will introduce you to Alzheimer’s disease, behavioural research, the mechanism of action of memory -enhancing drugs and the effects of sensory deprivation on brain development . In addition to what is provided in these pages there are links to research papers and reviews that are freely available to download if you are interested in reading further on a certain subject.
Alzheimer’s disease is named after the German psychiatrist Alois Alzheimer, who discovered the disease in 1906. It is a degenerative disease that affects over 25 million people worldwide and is characterised by the loss of neurons and synapses in the brain, causing atrophy of certain regions and reduction in brain size.
Early symptoms in patients with Alzheimer’s disease are recent memory loss, inability to learn new information, problems with attentiveness and abstract thinking. As the disease progresses it causes speech diffic ulties due to a reduced vocabulary, reading and writing difficulties, decreased motor coordination, impaired long-term memory recall and behavioural changes.
The following two short videos explore the probable causes of Alzheimer’s disease. Watch them both and answer the questions below.
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STUDENT MATERIALS
What is Alzheimer's disease? http://www.youtube.com/watch?v=9Wv9jrk -gXc&feature=related
Alliance for Ageing Research
(3 minutes 15 seconds)
YouTube video: Inside the Brain: Unravelling the Mystery of Alzheimer's
Disease [HQ] http://www.youtube.com/watch?v=NjgBnx1jVIU&feature=related
National Institute on Aging, National In stitute of Health and US Department of Health and Social Services
(4 minutes 22 seconds)
Questions
1. Name two of the brain changes that occur during Alzheimer’s disease .
2. In healthy people the enzymes alpha-secretase and gamma-secretase cut amyloid precursor protein (APP) into two fragments. These two fragments are then released from the neuronal membrane as shown in the second video. What are the two enzymes that cut APP in patients with Alzheimer’s?
3. What happens when beta-amyloid (short fragments of APP) is released in Alzheimer’s patients?
4. How are neurofibrillary tangles formed?
5. Using the internet or other up-to-date sources, describe the clinical symptoms of Alzheimer’s disease. How is the disease managed and what effect does this have on the families of Alzheimer’s patients?
6. Conduct your own investigation. What treatments are being investigated for Alzheimer’s patients as of 2010? Write 200–400 words on these current treatments and future directions.
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STUDENT MATERIALS
One of the most widely used paradigms for studying learning and memory in behavioural neuroscience laboratories is the Morris water maze. It was invented in Scotland (University of St Andrews) and was first published in
1981. The Morris water maze is designed for learning and memory experiments on rats or mice. It consists of a large pool of water containing a small hidden sub-surface platform. The task for the animal is simple: a single rat is placed in the pool and has to find the platform, thus escaping from the water. Subsequent experiments with the same rat can then test if it can remember the position of the platform using spatial memory alone.
Figure 1 Path taken (or swum) by a rat on the first attempt ( first trial) and the eighth attempt (eighth trial). By the eighth attempt the rat remembers where the platform is located. (Image from homepage of Dr Sandrine Thuret, UCL. More detail can be found at http://www.iop.kcl.ac.uk/departments/?locator=622&context=872 ).
Watch these two videos of rats in Morris water mazes.
Morris water maze vgao http://www.youtube.com/watch?v=_90ch04yk5Y&feature=related
(1 minute 33 seconds)
Morris water maze movie of a rat that will find the platform http://www.youtube.com/watch?v=_uco9kTr_jI&feature=related
(22 seconds)
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STUDENT MATERIALS
1. What is the difference in the performance of the two rats in the two videos?
2.
How is the rat’s performance measured?
3. Read the hypothesis and suggested experiments below.
Hypothesis: In each successive trial the rat will find the p latform more quickly.
Experiments:
1.
Put the rat in the water maze and time how long it takes to find the platform (trial 1).
2.
Allow the rat to rest for 60 seconds on the platform .
3.
Put the rat in the water again and time how long it takes to find the platform (trial 2).
4.
Allow the rat to rest for 60 seconds on the platform .
5.
Put the rat in the water again and time how long it takes to find the platform (trial 3).
6.
Continue until 11 trials have been completed.
7.
Perform this set of experiment for eight rats.
Results
Table showing the amount of time taken (seconds) for a rat to locate the hidden platform
Trial 1 2 3 4 5 6 7 8 9 10 11
Rat 1 90 68 44 32 25 21 22 8 12 11 12
Rat 2 85 65 48 35 30 19 18 24 15 5 10
Rat 3 86 70 46 48 21 21 15 21 20 9 5
Rat 4 102 85 51 56 24 20 23 25 11 14 9
Rat 5 96 81 52 57 27 20 26 18 15 8
Rat 6 108 80 48 71 26 23 14 14 18 7
14
6
Rat 7 94 72 47 45 27 18 12 13 10 10 12
Rat 8 107 75 56 36 22 21 11 10 5 16 8
Mean
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STUDENT MATERIALS
(a) Calculate the mean for all of the rats by trial number then plot the data in a graph.
(b) Can you accept or reject your hypothesis?
4. In a group discuss the paradigm and formulate a hypothesis that you would like to test using the Morris water maze. For this hypothesis, draw a flow diagram detailing the experiments that you would do to test the hypothesis.
Further reading
Morris RGM, Garraud P, Rawlins JNP, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297 , 681–683.
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STUDENT MATERIALS
Memory-enhancing drugs (also know as cognitive -enhancing drugs, smart drugs or in some cases nootropics) promote mental functions such as memory, cognition and concentration. There are several of these drugs on the market and they are used mainly to treat Alzheimer’s disease, Parkinson’s disease and attention-deficit hyperactivity disorder (ADHD), although some are becoming popular to aid academic study.
One of these drugs is methylphenidate (also known as Ritalin) , which is used to treat ADHD. Methylphenidate is an amphetamine derivative that works by increasing the level of the neurotransmitter dopamine (involved in reward) in the brain. Methylphenidate works by partially blocking the dopamine transporter (DAT) that removes dopamine f rom synapses back into the presynaptic neuron therefore causing an increase in dopamine in the synapse.
Methylphenidate also promotes the release of dopamine into the synapse.
This increased level of dopamine acts to decrease background firing rates and enhance the signal-to-noise ratio in target neurons, therefore improving taskspecific signalling and improving attention in ADHD patients.
The following table contains the results of an experiment that was designed to test the effects of methylphenidate on dopamine reuptake in rat brains over time. Three different dosages (10, 20 and 30 mg/kg) of methylphenidate have been tested. In addition, a placebo and an amphetamine are included in the study. Amphetamine is known to cause the release of dopamine from neurons but does not act in the same way as methylphenidate , which is thought to block reuptake of dopamine .
Rats of the same age were separated into five groups of ten and kept in identical conditions. Each of the five groups w as administered a specific dosage of methylphenidate, amphetamine or placebo at exactly the same time
(time 0), as follows:
Group 1: 10 mg/kg of methylphenidate
Group 2: 20 mg/kg of methylphenidate
Group 3: 30 mg/kg of methylphenidate
Group 4: 2.5 mg/kg of amphetamine
Group 5: placebo
The resulting dopamine levels shown in the table are the mean dopamine concentrations calculated from the groups of rats for each dosage of methylphenidate, amphetamine or placebo over 200 minutes.
Table 1 Results showing the effect of dosage of methylphenidate, amphetamine (mg/kg) and a placebo on dopamine levels at the synapse
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STUDENT MATERIALS
Time
(minutes)
Mean dopamine level in the synapse (nM)
MP 10 MP 20 MP 30 AMPH 2.5 Placebo
0
20
40
60
18
70
90
70
17
100
140
130
18
165
290
220
19
320
480
330
18
24
23
20
80
100
120
140
68
65
62
55
100
90
80
75
180
150
140
100
190
175
150
120
20
21
20
20
160
180
43
38
63
53
95
90
100
95
19
19
200 26 34 75 70 18
Key: MP 10, 10 mg/kg of methylphenidate; MP20, 20 mg/kg of methylphenidate; MP30, 30 mg/kg of methylphenidate; AMPH 2.5, 2.5 mg/kg of amphetamine.
Questions
1.
Make a graph showing the effects of methylphenidate on dopamine levels over time. Ensure that you give the graph a title, label all axes and include all of the data.
2.
Why has amphetamine been included in the study?
3.
Why has the placebo been included in the study?
4.
What is the relationship between increasing methylphenidate dosage and dopamine levels at the synapse in the first 40 minutes?
5.
Describe and explain the appearance of the lines in your graph ove r time.
Further reading
Kuczenski R, Segal DS (1997) Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine.
Journal of Neurochemistry 68 , 2032–2037.
Sahakian B, Morein-Zamir S (2007)
Professor’s little helper.
Nature 450 ,
1157–1159 (subtitle: The use of cognitive-enhancing drugs by both ill and healthy individuals raises ethical questions) .
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STUDENT MATERIALS
Read the following extract, which has been taken from a review paper written in 2010 about the effects of sensory deprivation on the reorganisation of neurons in the brain.
Merabet LB, Pascual-Leone A (2010) Neural reorganization following sensory loss: the opportunity of change. Nature Reviews Neuroscience 11 ,
44–52.
Traditionally, life without a particular sense has been viewed as
‘impoverished’ and many early theories postulated that sensory deprivation would have devastating effects on development, learning and cognitive behavioural performance. The ‘deficiency’ theory purports that a lack of perceptual sensory experience leads to an overall impairment in cognitive task performance given that proper multisensory integration can result only from the normal development of each sense. Howeve r, it is clear that blind and deaf individuals make striking adjustments to their sensory loss in order to operate effectively within their environment. Growing evidence from human and animal research indicates that these adaptations are inextricably linked to changes at multiple levels of the brain. In particular, it seems that these changes involve not only areas of the brain that are responsible for the processing of the remaining senses but also areas normally associated with the processing of the sensory modality that is lost. Furthermore, these changes might translate into behavioural skills and task performance levels that are equal and in certain cases even superior to those of individuals with intact sensory function. In other situations, however, n europlastic changes might be maladaptive, particularly in light of rehabilitative efforts that attempt to restore sensory function after it has been lost or fails to develop.
Thus, at one extreme there seems to be an underestimation of the adaptive potential of the brain, whereas at the other there is an assumption that neuro plasticity always leads to positive and advantageous outcomes.
Understanding the nature of these neuroplastic changes is important not just in terms of establishing the brain’s true adaptive potential but also in elucidating intervening developmental constraints and guiding future rehabilitation strategies. The study of neuroplasticity is an extremely broad field that is investigated at multiple levels from molecules, to neural systems, to behaviour.
Pioneering work in sensory deprivation showed that the brain is most receptive to change during an early period of postnatal life referred to as the critical period. Critical periods are specific to sensory modality, function and species. Furthermore, experimental evidence is consistent with the notion that the earlier the sensory loss, the more striking the neuroplastic effects.
© Learning and Teaching Scotland 2011
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STUDENT MATERIALS
The following is an extract from a research paper reporting the effect of visual sensory deprivation on brain d evelopment in cats.
Carriere BN, Royal DW, Perrault TJ, Morrison SP, Vaughan JW, Stein BE,
Wallace MT (2007) Visual deprivation alters the development of cortical multisensory integration. Journal of Neurophysiology 98 , 2858–2867.
To test the necessity of sensory experience for normal cortical multisensory development, cats were raised in the absence of visual experience from birth until adulthood, effectively precluding all visual and visual –nonvisual multisensory experiences. As adults, semichronic sing le-unit recording experiments targeting the anterior ectosylvian sulcus (AES), a well -defined multisensory cortical area in the cat, were initiated and continued at weekly intervals in anesthetized animals.
Below are the results from the study. The pie ch arts indicate the distribution of specific types of neurons in a specific region of the brain. The pie chart on the left shows the results from cats reared normally (in the light) whereas the pie chart on the right is that of sensory deprived cats reared i n the dark.
Figure 2 Effects of early visual deprivation in cats. Dark rearing alters the distribution of sensory responsive neurons in the anterior ectosylvian sulcus (AES).
(a) The lateral surface of the adult cat cortex, with the location of the AE S and the relative positions of its three major subdivisions : SIV, fourth somatosensory area;
FAES, auditory field of the AES; AEV, anterior ectosylvian visual area. (b) The distribution of sensory unresponsive, unisensory and multisensory mature AES neurons in normally reared and dark-reared animals. Values are rounded to the nearest per cent. AS, auditorysomatosensory; VA, visual -auditory; VAS, visualauditory-somatosensory; VS, visual-somatosensory.
1.
What does the somatosensory system do?
2.
Make two lists: one for the unisensory neurons and another for the multisensory neurons.
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STUDENT MATERIALS
3.
The table below organises the types of neurons into three categories : the visual system, the auditory system and the somatosensory system.
Some neuron types are only visually respon sive but other types are responsive to both visual and auditory stimuli. Fill in the percentages from the pie charts for normal and dark -reared cats but only if the neuron acts in that system. The first one has been done for you.
Visual
Auditory
Somatosensory
AS
VA
VAS
VS
Total
Visual system Auditory system Somatosensory
Normal DR Normal DR Normal DR
17% 12%
DR, dark-reared.
4.
Calculate the total percentage for each sensory system for both normal and dark-reared cats. What do you observe?
5.
How do you account for the differences between the normal and darkreared cats?
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