Psych 1XX3 –Behavioural Neuroscience (NSIII) Notes – Feb 2, 2010
Introduction to Cognitive Behavioural Neuroscience:
Role of Cognitive Neuroscientists:
Understand abstract mental processes in a neural framework.
Traditional paradigms used to study cognitive functions such as learning,
memory language, and problem solving are complemented by techniques such
as neuroimaging to trace the routes of neural processing.
Role of Behavioural Neuroscientists:
Understand the neural processes underlying behaviours such as reward, sexual
motivation, and feeding mechanisms.
Typically, these complex behaviours are simplified into component
behaviours that are modeled in simple animal systems to use the full range of
techniques available in neuroscience such as electrophysiology, pharmacology
and behavioural genetics.
Learning, Memory and Behaviour:
Focus of lecture will be on addressing the question of how you learn about the
world, remember information, and apply knowledge moving from lower to
higher levels of processing.
Head injuries: Depending on the severity and the region of the insult, deficits
can affect changes in planning, motor control, language production or even
induce coma or brain death.
However in some cases, rehabilitation can lead to miraculous recovery
allowing an injured person to regain lost abilities.
Everyday Neural Plasticity:
The brain is changing in every interaction with the environment. This
'everyday neural plasticity' allows your brain to adapt incoming stimuli and
rewire itself to optimize interactions with the outside world.
Beginning in the 1950s, researchers were well aware that environmental
influences can lead to enduring changes in complex behaviour that can be
Studies (Bingham and colleagues – 1952): demonstrated that exposure to
complex environments made animal subjects into better problem solvers.
However it was not until about a decade later that researchers realized the
importance of environmental experience on enduring changes in the physical
structure and functional organization of the brain.
In 1964, Bennett and colleagues compared the brains of rats raised in enriched
or impoverished environments. The enriched environment was like a little
piece of rat heaven, where the rats lived in social groups in a complex
environment filled with toys, ladders, tunnels and running wheels to explore.
In the impoverished environment, rats lived alone in small cages with access
to food and water only.
Researchers found that brains from the two groups were wired very
differently. The brains of rats exposed to the enriched environment had a much richer network of neurons with more dendrites and synaptic connections
compared to the brains of rats raised in the impoverished environment.
Another dramatic example of the role of environmental input on enduring
changes in neural structure comes from studies on maternal care in rat pups.
Meany and colleagues found that rats raised by mothers that engaged
extensively in maternal care behaviours (like licking and grooming) later grow
to become less fearful and less responsive to stress than do those raised by
mothers that do not engage as frequently in these maternal care behaviours.
These stress and fear behavioural traits observed in adulthood were matched
by measureable stress and fear changes in the brain including increased
expression of glucocorticoid receptors in the adult rat's hippocampus [Weaver
et al., 2004).
Many neuroscientists believe that similar effects may also be observed in
These experimental findings demonstrate that the brain is adaptive and can
detect contingencies between particular stimuli. This process of contingency
learning allows you to learn, remember and navigate through the world.
The first practical theory based on neuroscience principles came in 1949 from
a Canadian neuroscientist named Donald Hebb in his seminal work "The
Organization of Behaviour".
Hebb's theory described how connections between individual neurons can be
changed, and how combinations of connected neurons can be grouped
together as processing units. Hebb called these flexible units “cell-assemblies"
which could adapt to the constant adjustments necessary to direct the brain's
response to stimuli.
TF: All your complex thoughts can be built from the sequential activation of
Hebb's Law is often paraphrased as “neurons that fire together wire together."
A promising candidate mechanism for Hebbian learning is Long-term potentiation
LTP is the strengthening of the connection between two neurons and this effect
can last for an extended period of time; from minutes to a lifetime. It is also
sometimes referred to as an increase in synaptic efficacy, meaning a presynaptic
neuron becomes more efficient at generating a larger response in the postsynaptic
In the lab, this LTP can be measured by the change in amplitude of the EPSP.
LTP was first observed in 1973 by a PhD candidate studying the functional
circuitry of the hippocampus, which plays an important role in memory.
Terje Lomo made the startling observation that following activation by brief,
repeated bursts of high frequency stimulation, a single test pulse could make it
easier for adjacent cells to fire action potentials - an effect which could last for
several hours over the duration of an experiment.
This long term potentiation of signalling provided a cellular mechanism for the
synaptic change described in Hebbian Learning. There are several properties of LTP that make it such a promising candidate for
the neural basis of learning and memory.
LTP occurs very rapidly and is long-lasting, giving it a dynamic flexibility to
form new memories. Like memories, LTP is input specific, facilitating only the
synapses activated during the original stimulation.
The strong activity in Pathway 1 initiates LTP at the synapse, without initiating
LTP at the inactive synapse of Pathway 2.
Finally, LTP is associative, meaning that it can strengthen inputs from multiple
pathways if they are active simultaneously, as might naturally occur when two
related events are presented.
In this example, the weak stimulation of Pathway 2 alone does not trigger LTP,
However, when the weak input from Pathway 2 occurs together with the strong
input from pathway 1, both sets of synapses are strengthened.
Mechanism of Classical Hippocampal LTP:
Lomo's original observations were made using an in vivo hippocampal
preparation, which limited the techniques that could be used in an experiment.
However; with the development of an in vitro tissue preparation, a fresh
hippocampal tissue slice could be kept alive in a dish, allowing many new
experimental tools to be used.
The Mechanism of LTP:
When the neurotransmitter glutamate is released from the presynaptic neuron it
binds to the AMPA receptor, which is in fact both a receptor and an ion channel.
This binding causes the channel to open, allowing the flow of positively-charged
This depolarizes the post-synaptic cell moving it away from its' -70 mv resting
potential, and closer to the -50mv threshold for an action potential to occur.
TF: binding of glutamate at the AMPA receptor alone can be sufficient to cause a
short-lived EPSP. Diagram shown on next page. Classical LTP begins with the presynaptic release of the neurotransmitter
glutamate, which can bind to the AMPA receptor and another receptor called the
Glutamate binding to the AMPA receptor is associated with the normal synaptic
transmission that you are already familiar with
Glutamate binding to both its NMDA and AMPA receptor types is associated
with the induction or development of LTP (Image below)
Glutamate binding to both AMPA and NMDA receptors turns out to be important
for another key player necessary for LTP induction.
The concentration of positively charged calcium ions inside the postsynaptic cell
must exceed a critical threshold. This process of calcium ion flow can only occur when glutamate binds to the
NMDA receptor. However, at the resting state, the NMDA receptor-channels are
blocked by magnesium, preventing calcium from entering the cell. (Image below)
So what's a postsynaptic cell to do? Fortunately, successive EPSPs via the binding
of glutamate to the AMPA receptors, leads to sufficient depolarization that
unblocks the Mg. This allows calcium to enter the post-synaptic cell and induce
This takes a lot of coordination. Calcium entry requires both presynaptic and
postsynaptic activity to occur.
The depolarisation of the postsynaptic neuron must be perfectly timed with the
firing of the presynaptic neuron to allow the calcium channel to fully open. The
requirement of this coincident activity is what makes LTP so compellingly related
to learning. (Diagram shown below) Why does calcium entry lead to a strengthening of the synaptic connection?
Calcium entry into the postsynaptic neuron has a number of complex effects, but
one important result of this activity is to promote the expression of more AMPA
receptors in a specific region of the post-synaptic neuron.
A specific synapse on the postsynaptic neuron becomes more sensitive to
glutamate release from a specific presynaptic cell, strengthening the connection.
Diagram shown below.
LTP and LTD:
The increased expression of AMPA receptors in the post-synaptic cell can last for
hours, weeks and even months in lab preparations.
Just as there are IPSPs to counter EPSPs, another mechanism, called long-term
depression (LTD), exists to decrease the sensitivity of synaptic connections,
Together, research on LTP and LTD help to explain why neurons that fire
together wire together
A Functional Role for LTP:
How is LTP directly involved in behaviours associated with learning and
Simple Circuits for Memory:
Eric Kandel has been responsible for much of the pioneering work in linking
behaviours associated with learning and memory with synaptic changes in the