May 1, 2008
Dr. Eliot
Learning & Memory
Lise Eliot, PhD
May 1, 2008
Related Reading: Purves Chapter 31
Thanks to: Elliott Ross MD, U. Oklahoma for many of these concepts and several slides
Lecture topics
Types and mechanisms of learning
Temporal organization of memory
Explicit vs. implicit memory
Amnesia
Neuroanatomy of explicit memory
LTP as storage mechanism
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May 1, 2008
Dr. Eliot
Learning and Memory
Learning is the process of acquiring
information about the world.
Memory is the process by which that
information is encoded, stored, and later
retrieved.
Include both conscious and unconscious
forms: motor and cognitive skills, facts,
experiences, emotional responses,
perceptual changes, habits
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Types of learning
Non-associative:
Habituation
– decreased responding to a
repeated stimulus
Sensitization
─ increased responding after a
highly salient stimulus (e.g.,
hyperalgesia)
Associative (timing is critical):
Classical conditioning (e.g. Pavlov’s dog)
– pairing two stimuli alters response to the neutral one
– can be appetitive or defensive
Operant or instrumental conditioning (Skinner box)
– pairing a response with reward or punishment
– especially prominent in motor learning
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May 1, 2008
Dr. Eliot
Emotional
conditioning:
Amgdala
Simultaneous input of neutral
sensory stimuli (context) and
reinforcing stimuli (pleasure
or pain) leads to long-term
changes in the output of
principal amygdala neurons,
altering behavior.
Learning can be blocked by
infusing NMDA antagonists
into the amygdala,
suggesting the plasticity is of
the Hebbian LTP type.
Purves 28.6
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Memory: Temporal categories
1-2 years)
(years
Slide courtesy of Elliott Ross MD
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May 1, 2008
Dr. Eliot
Taxonomy of long-term memory
(Purves 31.1)
(skills and habits)
Medial temporal lobe
Various cortical and
subcortical structures
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Explicit vs. implicit memory
EXPLICIT
IMPLICIT
Declarative (verbal)
Non-declarative (Procedural)
Conscious
Unconscious
Reflective
Reflexive
Memory of “what”
Memory of “how”
Single trial learning
Repeated training
Flexible, association of
many bits of information
Rigid, closely tied to original
stimulus conditions
Unreliable (distortion,
forgetting)
Reliable
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(skills and habits)
 
 
 
 
 
 
 
 
May 1, 2008
Dr. Eliot
Amnesia
Loss of long-term, explicit memory, with no
loss of general intelligence.
Anterograde : unable to form new memories
after damage.
Retrograde : loss of memories for events that
took place before damage.
Short-term memory (e.g. working memory or
digit span) unimpaired.
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ICTUS
e.g.: trauma, stroke, seizure
Retrograde
Amnesia
Anterograde
Amnesia
TIME
Slide courtesy of Elliott Ross MD
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e.g.: trauma, stroke, seizure
May 1, 2008
Dr. Eliot
Retrograde amnesia
Memory can be temporarily disrupted by a blow to the head or other
trauma, such as electroconvulsive treatment (ECT).
Similar disruption is produced in experimental animals by drugs that
depress neural activity or protein synthesis.
During the consolidation from
short- to long-term storage,
memories are especially labile.
(Kandel 62.11)
Sensory
information
Short-term
memory
Long-term
memory
Experiment at right shows that ECT
selectively abolishes the most recent
memories (those still being consolidated).
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H.M.
(Blumenfeld, 18.16)
27-year-old male had bilateral
resection of medial temporal lobes in
1953 to relieve unremitting seizures.
Complete anterograde amnesia.
Several years’ retrograde amnesia.
Spatial orientation problems.
No deficits in remote memory, short-
term memory, language, or IQ.
(Purves Box 31C)
MRI in 1997 confirmed bilateral loss
of hippocampal formation,
amygdala, uncus, and some of the
parahippocampal gyri.
Excised area is indicated by the white
dotted line. A similar amount of tissue
was resected from both sides of the
brain. (Coronal views, see Purves p. 801.)
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May 1, 2008
Dr. Eliot
HM: T1-weighted coronal MRI
H.M.
Age-matched control
MMN = medial mammillary nucleus; ; A = amygdala; H = hippocampus; cs =
collateral sulcus; PR = perirhinal cortex; EC = entorhinal cortex; [S. Corkin et
al., Journal of Neuroscience , 17:3964-79 (1997)].
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Normal implicit memory in H.M.
(Kandel 62.2)
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May 1, 2008
Dr. Eliot
Priming
Another type of implicit memory
Subjects presented with a list of
words, then tested later:
– to recall as many as possible
– to complete a set of three-letter
stems
Temporal lobe amnesics perform
normally on priming task but
cannot consciously recall any
words from the list.
Priming is an important
component of all learning;
information has an impact even
when we are unaware of it.
(Kandel 62.3)
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Patient R.B.
Ischemia following cardiac
arrest and coronary
bypass at age 52.
Memory deficit
qualitatively similar to
H.M., but much less
severe.
Died at age 57.
Lesion specific to area
CA1 bilaterally: almost
total loss of pyramidal
cells, probably due to
excitotoxic cell death
Top: normal hippocampus.
Bottom : Destruction of CA1 cell
layer in a similar amnesic patient
following an ischemic episode
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May 1, 2008
Dr. Eliot
Medial temporal lobe anatomy
(Blumenfeld 18.6)
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Medio-
dorsal
thalamus
Sylvius4
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May 1, 2008
Dr. Eliot
How memories are stored
There is no single “memory center” in the brain. Memories are stored as
distributed sets of synaptic changes .
Nondeclarative memories are stored within the same circuits that carry out
the behavior—e.g., cerebellum, basal ganglia, amygdala, motor cortex.
Declarative memories uniquely depend on the hippocampus and surrounding
medial temporal lobe.
– During consolidation, the medial temporal lobe essentially acts as the brain’s
recording device. It creates long-term memories but does not itself warehouse
them.
– Another analogy is a temporary way-station : after the consolidation period (1-2
years, based on studies of retrograde amnesia), the hippocampus ships memories
out to other cortical sites for permanent memory storage, such as Wernicke’s area
for word meanings, or inferior temporal cortex for familiar faces.
– The hippocampus and surrounding temporal cortex works by binding together
information from many different sites, creating a multi-dimensional representation of
a person, object, word, or event. As a highly-excitable side-loop , it is thought to
maintain experience-based activity in sensory and association cortices until a more
permanent trace is consolidated through long-term synaptic plasticity.
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Widespread hippocampal connections
(Purves 31.11)
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How memories are stored
May 1, 2008
Dr. Eliot
LTP review
(Purves 8.8)
Hippocampal LTP is one
mechanism by which
salient stimuli (e.g., the
different sensory
components of an
experience) may become
bound together in a long-
lasting way.
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Properties of LTP
LTP is both synapse-specific , and associative , both ideal properties for a
mechanism of memory storage. Its induction depends on NMDA-R activation.
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May 1, 2008
Dr. Eliot
Long-term depression (LTD)
If long-term memory storage relied exclusively on LTP, we
would soon “use up” our hippocampal plasticity--that is,
maximally potentiate all existing synapses, leaving no room for
additional storage.
LTD is a long-lasting decrease in synaptic efficacy triggered by
low-frequency or specifically unpaired input.
LTD is not , however, the mechanism of “forgetting.” Both LTP
and LTD have been implicated in long-term memory storage.
(Recall the role of cerebellar LTD in motor learning.) Whether a
specific synapse needs to be strengthened or weakened during
learning depends on its exact role in the circuit, as well as its
previous history of activity.
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Summary: Memory & amnesia
Short-term
a mixture of memory types including:
– “immediate memory” (essentially the sensory trace of something you just
heard, saw, felt, etc.)
– “working memory” (conscious holding of information to carry out a task)
lasts for only seconds or until you stop rehearsing
generally survives all but the most extreme brain injury or disease (though
working memory more vulnerable to PFC damage)
Recent
memories of events from the “recent” past – from minutes up to a few years
storage and retrieval depend on medial temporal lobe and medial diencephalic
structures
damage to these areas produces both anterograde and retrograde amnesia
Remote
memories of events from early in one’s life
resistant to damage of medial temporal lobe and medial thalamus
stored as distributed but linked sets of synaptic changes in the cortex
oldest memories preserved longest in dementia and other amnestic syndromes
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