Week 4: Learning Outcomes
By the end of Topic 1 you will be able to: Understand
the process and properties of LTP at excitatory,
glutamatergic synapses Describe the
molecular mechanisms underpinning LTP induction,
consolidation and maintenance Explain, with
appropriate examples, how learning and memory can be
studied in rodents Describe the evidence
indicating that synaptic plasticity is fundamentally
important for memory By the end of Topic 2 you will be
able to: Understand that synapse structure is dynamic
and a critical part of how information is encoded in the
brain Explain that a number of disorders of the brain are
associated with altered neuronal and synaptic
morphologies, which may contribute to the disease state
Understand that several lines of evidence indicate that
neuronal wiring may be altered in the brains of individuals
with SCZ Describe that a
number of genetic factors associated with SCZ encode for
proteins found at synapses Understand that it is possible to
model the role of synaptic proteins to gain insight into how
dysregulation of these proteins may result in altered
BIOLOGICAL dendritic spine number, and therefore altered neuronal
wiring By
the end of Topic 3 you will be able to: Describe the
FOUNDATIONS OF
way that synapses are modified by activity and experience
Understand how spontaneous activity segregates the brain’s
response to sensory stimuli Understand how
sensory experience integrates the brain’s response to
MENTAL HEALTH sensory stimuli Understand how sensory
deprivation re-balances the brain’s response to sensory
stimuli Understand how inhibition shapes
critical periods for development
WEEK FOUR Appreciate how scientific insight into the impact of
activity, experience and deprivation on the brain informs us
about the causes of neurodevelopmental disorders
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, This week's topics are:
Learning, memory and synaptic plasticity
When wiring goes wrong
The effects of activity, experience and deprivation on the nervous system
Welcome to Week 4.
Building on the concepts introduced in the first 3 weeks, week 4 explores how the brain works to produce
complex or higher executive functions; our current theories on how information and memories are stored in
neural networks, and finally how aberrant wiring of the brain is linked with mental health issues.
Topic One: Learning, memory and synaptic plasticity Part One
Part One: Overview
Neurons are connected by synapses. And these synapses are terribly complicated. They can change
their properties over time and this change in properties actually is called synaptic plasticity.
Synaptic plasticity is thought to be very important for learning and memory.
Definition of synaptic plasticity
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,Synaptic plasticity is a history dependent change in synaptic transmission. Synaptic transmission can change in
different ways as you could imagine. It could increase or it could decrease. And the change in synaptic
transmission could be short-lasting or long-lasting.
Accordingly, we distinguish therefore between a potentiation or a depression of synaptic transmission. And we
qualify over time course as short or long lasting. We could have a long-term potentiation, that is LTP. Or we
could have long-term depression, that is LTD as we are calling for that. Or we could have short-term
potentiation or short-term depression.
Such changes in synaptic transmission may very well be suited to store information of the brain. The inputs have
triggered then a change in synaptic transmission and that has changed. That is a very good mechanism possibly
to store information. The main excitatory neurotransmitter in the brain is glutamate. There is of course also
plasticity at inhibitory synapses. For example, GABAergic synapses.
Measurement of synaptic plasticity
Most forms of synaptic plasticity have been studied in the hippocampus. This slide shows the rodent’s
hippocampus. If a rodent brain has a neocortex where it is not very much foliated in comparison to human
cortex, it is rather smooth and flat. And underneath you see like a cashew nut here lining the hippocampus rather
big in relation in neocortex in rodents. And when you make a slice through the hippocampus, you see this
beautiful anatomy. You see the so called tri circuitry. So what you see are granule cells in the dentate gyrus with
granule cells are innervated by the so – called perforant path, which is PP in this diagram. The perforant path
comes from entorhinal cortex.
When the perforant path involves with granule cells. Which have as axons with so-called mossy fibres, MF in
this diagram, and for mossy fibres innervate C3 pyramidal neurons. These are pyramidal neurons because the
neurons have a shape like a pyramid.
So we see C3 pyramidal neurons send the axons for so called Schaffer collaterals on the C1 neurons. These are
C1 pyramidal neurons. Now synaptic plasticity has been studied between C3 and C1 neurons. First of all
because of its beautiful, simple anatomy. But secondly and very importantly the hippocampus is fundamentally
important for learning and memory. There is this famous case of patient H.M. Patient H.M suffered from severe
epilepsy and when the 50s surgeons decided to remove the focus of the epilepsy in this patient H.M.
And what they did is they lesioned this here brain area that produced the epilepsy and that brain area was
included the hippocampus. So the lesion treatment worked for the treatment of epilepsy, but it left the patient
with severe memory impairment. And since then basically people have started to realise that the hippocampus is
particularly important for learning and memory.
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, It is particularly important for the types of memory we are aware of it, so – called declarative memory. For
example, you may know who’s the prime minister in your country or you may know who is Boris Becker, my
favourite tennis star. So kind of such memories depend on the hippocampus so now there was great motivation
to study synaptic plasticity in the hippocampus because its importance for learning and memory and also
because of its simple neural anatomy.
How do you study synaptic plasticity in the hippocampus?
You have to used electric stimulation electrode. So the stimulation electrode can give you the electric impulses
that evoke action potentials on axons. So a stimulation electrode is placed onto the Schaffer collaterals to
produce action potentials, which propagate down the axon to ultimately induce neurotransmitter release. And
then you need a recording electrode to measure synaptic potentials. So therefore what you can do here, you can
repeatedly stimulate and record the synaptic potentials or synaptic currents.
Different forms of synaptic plasticity
Now when you do this you may discover different forms of synaptic plasticity as we have
classified in-principle at the beginning. So for example, in the left panel you see an
example for short-term potentiation, or the acronym is STP. So what is shown here or
what is plotted here over time, the excitatory postsynaptic potential, or EPSP. So the
EPSP is a measure of synaptic transmission of excitatory synaptic transmission. So when
you stimulate once in a while you get this dot basically this black dot. So stimulating
once in a while gives you a constant synaptic transmission at 100% level. But then if you
provide a high frequency stimulation, which is indicated by the green arrow here. Then
after the high frequency stimulation, now stimulating once in a while shows you more
synaptic transmission in the increased EPSP. And in this case we increased the EPSP, the
increase last only for a short period of time. So over time it declines and it goes back to
the so-called baseline.
So this phenomena is called short-term potentiation. Normally it lasts for about 30
minutes and
it depends, as I said, on a high frequency stimulation. So as if this synapse remembers
that it
had experienced a high frequency stimulation. The next, in the middle, is long-term
potentiation, another form of synaptic plasticity. And the difference now if you compare
the curves, is that this type of potentiation lasts longer and it actually has initially a
transient increase. This is the transient increase because actually in this case, we have
some short-term potentiation that precedes long- term potentiation. So the short-term
potentiation declines over time and then you see synaptic transmission remains at a
higher level.
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