Neural Basis of Cognition
Lecture 6
Learning and Memory, Part II
• Extensive hippocampal damage leads to amnesia
• The hippocampus receives highly preprocessed
input from multiple areas and projects back to
• The hippocampus is activated during memory
encoding, consolidation, and retrieval
• Pre-existing memories are left intact by
hippocampal damage
• Memories are thought to be stored in the areas
that initially processed given information
• What about working memory?
• Are any other areas of the brain related to
• What is the relationship between memory and
• Given the relatively stable “neural wiring” in
the brain, how is memory possible?
What about working memory?
Working Memory
• Fulton, 1935: Frontal cortex lesions and their
effect on the spatial delayed-response task
with dogs
– Food is put in one of several wells and each well is
closed; after some delay, the animal is given the
opportunity to choose a well
– Frontal cortex lesions destroyed the ability to
remember which well contained food
Working memory
• Dorsolateral prefrontal cortex (DLPFC)
Working Memory
• Golman-Rakic: DLPFC lesions and their effect on an
occulomotor version of the delayed-response task with
– While the monkey looks at a fixation point, one of eight
target locations is briefly lit; after the light goes off, after
some delay the monkey must saccade to the target
– DLPFC lesions severely impair performance on this task
– Neurons in the DLPFC continue firing during the delay
– This neural activity is absent on trials in which the monkey
makes a mistake
Working Memory
• Single cell recording studies show that the
exact region of the DLPFC that holds
information online varies depending on the
nature of that information
– DLPFC: locations
– Lateral PFC: objects
Working Memory
• Loss of working memory does not cause
• Patient KF:
– Could not hold online short strings or digits
– Could learn word lists or stories
Are any other areas of the brain related to
Prefrontal Cortex (PFC)
• Ventrolateral PFC activates during encoding of
long-term memories
– Lateralized
– Activates regardless of conscious intent to encode
memories (intentional vs. incidental encoding)
– Exhibits subsequent memory effect
Prefrontal Cortex (PFC)
• Other regions of the PFC activate during memory
• Patients with PFC damage tend to confabulate
(generate narratives that include false memories)
and an increased number of false positives in
recognition-memory tasks
– This implies that the PFC is involved in organizing and
monitoring memory retrieval
• PFC activation during memory retrieval is
Prefrontal Cortex (PFC)
• There is activity in posterior PFC during
memory retrieval but this activity appears to
be related to retrieval attempt rather than
• Greater activation for more poorly encoded
• Amount of activation is independent of
whether the item is successfully remembered
Prefrontal Cortex (PFC)
• Anterior frontopolar PFC region activates
during retrieval and tends to be right
lateralized regardless of the type of
• Degree of activation does not vary with
difficulty of information retrieval
• Activation is more common in free recall or
cued recall tests
Prefrontal Cortex (PFC)
• In conclusion:
– The PFC seems to be involved in strategic and
executive aspects of memory.
– The PFC appears to aide in organization, selection,
monitoring, and evaluation of processing that
occurs at both encoding and retrieval rather than
in storage/retrieval of the actual contents of
memory of experience
Are any other areas of the brain related to
Left Parietal Cortex
• General role in memory retrieval, regardless of
nature of content or of modality
• More activation during retrieval of “old”
information than of “new” information
• Correct recall is associated with parietal cortex
activity independent of the nature of the
remembered material, suggesting that this
activity reflects retrieval success
Are any other areas of the brain related to
What is the relationship between memory and
• Lesion of the amygdala but not of the
hippocampus precludes fear conditioning but
not the memory of the conditioning
• Lesion of the hippocampus but not of the
amygdala precludes the memory of
conditioning but not the fear conditioning
• Lesion of the hippocampus and of the
amygdala precludes both
• Normally, emotional content of an experience
results in enhanced recall
• Lesion of the amygdala but not of the
hippocampus destroys this enhancement but
not the appreciation of emotion during the
emotional experience itself
• Interference of the function of the amygdala
via beta-adrenergic antagonists temporarily
caused the same effects as amygdalic lesion
Given the relatively stable “neural wiring” in the
brain, how is memory possible?
Long-tem potentiation (LTP)
• 1894: Ramon y Cajal suggests the strengthening of
connections between existing neurons as a possible
mechanism for memory formation
• 1949: Hebb: “When an axon of cell A is near enough to
excite a cell B and repeatedly or persistently takes part
in firing it, some growth process or metabolic change
takes place in one or both cells such that A's efficiency,
as one of the cells firing B, is increased.”
• 1966: Lomo discovers that tetanic stimulus of a neuron
causes it to subsequently cause larger EPSPs, what is
now called long-term potentiation (LTP)
• If neuron A fires before neuron B fires: LTP
• If neuron A fires after neuron B fires: LTD
• Blocking NMDARs prevents LTP
• Asymmetric learning rule
• What could be the mechanism behind the
induction of LTP/LTD?
protein kinase II (CaMKII) is
localized in the postsynaptic
density (PSD) and is necessary
for LTP induction
• Strong Ca2+ influx leads to phosophorylation
of CaMKII, which leads to an increase in the
number of AMPA receptors in the cell
membrane, inducing LTP
• “a phosphatase (PP2A) switch,… together with a
kinase switch [forms] a tristable system. PP2A can
be activated by a Ca2+-dependent process, but
can also be phosphorylated and inactivated by
CaMKII. When dephosphorylated, PP2A can
dephosphorylate itself.”
• “the kinase activity is high in the LTP state; the
PP2A activity is high in the LTD state and neither
activity is high in the basal state.”

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