Psyc2190
Physiological Psychology
LT8: Memory
Prof. Chun-Yu TSE
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Types of Learning
• Perceptual learning
– Ability to recognize/identify/categorize/make sense of
some stimuli/situation/environment
• Stimulus-response learning: Ability to learn to perform
a particular behavior when a particular stimulus is
present
– Classical conditioning
– Operant conditioning
• Motor learning, e.g., riding a bike, playing the piano
• Relational learning, e.g., spatial learning, episodic
memory
Example of Perceptual Learning
All sensory systems capable of perceptual learning.
Involves changes in appropriate sensory association cortex.
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Perceptual Learning
Learning enables us to adapt to our environment and
to respond to changes in it
• Perceptual learning involves learning to recognize
things, not what to do when they are present
• Perceptual learning can involve learning to
recognize entirely new stimuli, or it can involve
learning to recognize changes or variations in
familiar stimuli
• Facilitates processing but does not change
response to stimulus (c.f. habituation)
Classical Conditioning
• Hebb rule: if a synapse is active about the time the postsynaptic neurons fires,
that synapse will be strengthened, i.e., neurons that fire together, wire together
• Cellular basis of learning involves strengthening of synapse that is repeatedly
active when postsynaptic neuron fires
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1. Established by pairing a
neutral stimulus (the CS;
e.g. tone) with an aversive
stimulus (the US, e.g.
shock)
2. Information about the CS
and the US reaches the
lateral nucleus of the
amygdala
3. Lateral nucleus projects to
the central nucleus, which
triggers the emotional
response
4. Weak synapse between
the CS and the emotional
response are strengthened
5. Involves LTP in the lateral
amygdala
Operant Conditioning
• Organisms learn responses by
operating on the environment,
such responses are called
‘operants’
• If response à good
consequence, then response
more likely to occur next time
• If response à bad
consequence, then response
less likely to occur next time
• Focus on what FOLLOWS
response and how that affects
likelihood of future responses
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Role of the Basal Ganglia in Instrumental
(Operant) Conditioning
There are two major pathways between sensory association
cortex and motor association cortex
• Direct transcortical connections (connections from one area
of the cerebral cortex to another)
• Initial acquisition of the behavior
• Connections via basal ganglia and thalamus
• Automatic procedure
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Dopamine in Reinforcement
•
•
•
Mesolimbic
dopaminergic
system
Nucleus
Attention
accumbens is
activated by
reinforcer
Dopamine induces
LTP and synaptic Basal Ganglia
plasticity
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Learning & Memory
(Motor)
Squire, L. & Zola, S. (1996). Proceedings of the National Academy of Sciences, 93, 13515-13522.
Neural Mechanism in Learning
• Repeated exposure to the stimuli/stimulation
lead to changes in neural responses
• Long-term potentiation (LTP)
– Long-term increase in excitability of neuron to
particular synaptic input caused by repeated highfrequency activity of that input
– Non associative LTP
• Associative long-term potentiation
– Long-term potentiation in which concurrent
stimulation of weak and strong synapses to a given
neuron strengthens weak ones (Hebb rule)
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Gray’s anatomy
Fornix
Preparation of a human hippocampus and fornix
alongside a sea horse (Laszlo Seress, 1980)
http://morphonix.com/
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Non-associative LTP
Burst stimulation of
axon in perforant path
Single pulse
stimulation
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Both NT and
depolarization
take place at the
same time
Non-associative LTP with repeated
simulation
Earlier EPSP triggers AP at axon
hillock and “back fire” (dendritic
spikes
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LTP
Release of neurotransmitter and depolarization of postsynaptic
membrane had to occur at same time
NMDA receptor
• Specialized ionotropic glutamate receptor that controls calcium
channel that is normally blocked by Mg2+ ions
• Involved in long-term potentiation
• requires some sort of additive effect (presence of glutamate and
depolarization of post-synaptic membrane)
• Both ligand/neurotransmitted gated and voltage gated Ca2+
channel
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Cellular mechanisms of LTP:
postsynaptic changes
1. Repeated glutamate excitation of AMPA receptors
depolarizes the membrane
2. The depolarization removes magnesium ions that had
been blocking NMDA receptors
3. Glutamate is then able to excite the NMDA receptors,
opening a channel for calcium ions to enter the neuron
4. Entry of calcium through the NMDA channel triggers
further changes
5. Activation of CaMKII (Type II calcium-calmodulin kinase)
sets a series of events in motion
6. More AMPA receptors are built and dendritic branching
is increased
7. These changes increase the later responsiveness of
the dendrite to incoming glutamate
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Cellular mechanisms of LTP:
presynaptic changes
• Changes in the presynaptic neuron can also cause LTP
• Extensive stimulation of a postsynaptic cell causes the
release of a retrograde transmitter (nitric oxide) that
travels back to the presynaptic cell to cause the following
changes:
– Decrease in action potential threshold
– Increase neurotransmitter release
– Expansion of the axons
– Transmitter release from additional sites
Associative LTP
With weak
stimulation at
electrode 1
Repeated
stimulation
at both
electrodes
With weak
stimulation at
electrode 1
With strong
stimulation at
electrode 2
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This synapse can
trigger action
potential with a
weak stimulation
Due to synaptic
plasticity
Mg2+ is ejected
from NMDA
receptor
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Mechanisms of Synaptic Plasticity
AMPA
receptor
Ionotropic glutamate receptor that controls sodium channel
CaM-KII
Type II calcium-calmodulin kinase, an enzyme that must be
activated by calcium; may play a role in establishment of
long-term potentiation
Nitric
oxide
synthase
Enzyme responsible for production of nitric oxide (NO),
which is a retrograde messenger to the presynaptic axon
terminals to induce presynaptic change (e.g., increase
glutamate release)
When open, it produces EPSPs
Leading to change in the number of AMPA receptor, size and shape of dendritic spines
Long-term depression (LTD)
• Long-term decrease in excitability of neuron
to particular synaptic input caused by
stimulation of terminal button while
postsynaptic membrane is hyperpolarized or
only slightly depolarized
• Reduced number of AMPA receptors
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Amnesia
(Hippocampus)
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Memory Systems
Anterograde
Amnesia
Semantic
Episodic
Squire, L. & Zola, S. (1996). Proceedings of the National Academy of Sciences, 93, 13515-13522.
H.M. was taught to trace
between two outlines of a
star while viewing his hand
in a mirror.
He improved considerably
with each fresh test although
he had no recollection that he
had ever done the task
before.
The graph plots the number
of times, in each trial, that he
strayed outside the outlines
as he drew the star.
H.M. has pockets of intact memory:
Manual skills: Corkin, S., (1968). Acquisition of motor skill
after bilateral medial temporal lobe excision.
Neuropsychologia, 6, 255-65.
Cognitive skills: Cohen, N.J. & Squire, L. (1980).
Preserved learning and retention of pattern-analyzing
skill in amnesia: Dissociation of knowing how and
knowing that. Science, 210, 207-9.
Priming: Warrington, E. & Weiskrantz, L. (1973). The
effect of prior leaning on subsequent retention in
amnesic patients. Neuropsychologia, 20, 233-248.
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Relational Learning
Role of the Hippocampal Formation in
Consolidation of Declarative Memories
• Patients with damage to the hippocampal
formation can remember events that happened
before their brain damaged, and their short-term
memory is relatively normal
• But hippocampal formation clearly plays role in
process through which declarative memories are
formed
Relational Learning
Spatial Memory
• People with anterograde amnesia are unable to
consolidate information about location of rooms,
corridors, buildings, roads, and other important items
in their environment
• Bilateral medial temporal lobe lesions produce most
profound impairment in spatial memory, but significant
deficits can be produced by damage that is limited to
right hemisphere
• London Taxi driver showed a larger right hippo than
control!
Winners of 2014 Nobel Prize in Medicine
The Nobel Assembly said today (October 6, 2014): “The discoveries of John O’Keefe,
May-Britt Moser and Edvard Moser have solved a problem that has occupied
philosophers and scientists for centuries – how does the brain create a map of the space
surrounding us and how can we navigate our way through a complex environment?
“The discovery of the brain’s positioning system represents a paradigm shift in our
understanding of how ensembles of specialised cells work together to execute higher
cognitive functions. It has opened new avenues for understanding other cognitive
processes, such as memory, thinking and planning.”
Place Cell
• Recorded activity of
individual pyramidal cells
in hippocampus as animal
moved around the
environment
• Found that some neurons
fired at high rate only
when rat was in a
particular location
• Different neurons had
different spatial receptive
fields
• They responded when the
animals were in different
locations
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•Since discovery of place cells,
researchers found that
hippocampal region also
contains grid cells, head
direction cells, and border
cells, all found in entorhinal
cortex (Derdikman and Moser
; 2010)
•Grid cells show evenly
spaced, crystal-like coverage
of entire environment in
which animal is located
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Border cells fire when animal
is near one or more
boundaries of environment,
such as walls of a box
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Voxel-based morphometry findings
©2000 by National Academy of Sciences
Maguire E A et al. PNAS 2000;97:4398-4403
Memory in Action
A mother was suffering from "forgotten baby syndrome" when her young son died in a hot car, an Australian
inquest has heard.
Expert's evidence
A psychologist told the inquest he believed Ms Zunde suffered a memory lapse called "forgotten baby syndrome".
"If you are capable of forgetting to post a letter, you are capable of forgetting to take your baby out of the car,"
said Matthew Mundy, an associate professor at Monash University.
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