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The Neuroscience of Memory
MARISSA DI GIOVINE, PGY5
DR. RAPIN’S SEMINAR SERIES
FEBRUARY 2013
Outline of Presentation
 Definition of memory
 Clinical Case – H.M. and how he changed memory
 Approach to memory
 Cellular level of memory
 Short-term memory
 Learning from Amnesia
Learning and Memory
 “Learning is the process of acquiring new
information, while memory refers to the persistence
of learning in a state that can be revealed at a later
time.”
-Larry Squire, UCSD, 1987
H.M.
 Epilepsy began when he was 10 years old, and progressed
to become intractable, so at the age of 27, in 1953, he had
bilateral medial temporal lobe resections
 His already above-average IQ actually increased post-op
(2/2 less seizures?), but he became severely amnesic with
almost no other neurologic deficits
(1) intact perceptual, motor, and cognitive functions, (2) intact
immediate memory, (3) severe and global anterograde
amnesia, (4) temporally graded retrograde amnesia, (5) spared
remote memory.
 Showed a clear dissociation between fully intact
perception and cognition versus severely impaired
memory
Approach to Memory
 Short term v. long term memory
 Recall in milliseconds/seconds/minutes v. days/years
 4 C’s of memory:
 Connection – cellular level of memory
 Cognition – memories at a psychological level. Includes
behavioraism (all learning is 2/2 conditioned responses) v.
congitivism (complex phenomena such as insight and
inference required for complex learning)
 Compartmentalization – memory is distributed in wide but
discrete areas of the brain
 Consolidation – are memories at first labile, then become
resistant to loss?
Connection
 The Neuron  Electrotonic Conduction  Action Potential
 Synaptic Transmission
Connection: Habituation and Sensitization
 Simplest form of learning/memory
 Non-associative learning
 Kandel et al: first described these by studying the
Aplysia, a large sea snail


Habituation: with repeated stimulation, lessened response
Sensitization: increase in response to a stimulus

The same set of cells can mediate both habituation and
sensitization (two different forms of learning/memory)
Connection: Classical Conditioning
 Pavlov won a Nobel Prize in 1904 for his work in this
topic
 Can also form in Aplysia (a simple nervous system)

There is a change in protein synthesis at this level
 Associative learning: develops an association
between two stimuli

Pavlov’s dogs: 1st/conditioned stimulus = bell,
2nd/unconditioned stimulus = food; conditioned response =
salvation when hearing the bell
Connection: Long Term Potentiation (LTP)
 Named by Lomo, who was studying cells in the
hippocampus (specifically CA1)
 Found that tetanus-inducted changes (repetitive high-
frequency stimuli of one pathway causing a greater
population spike) lasted for several hours


Called this “long-term potentiation”
Others also found evidence of hippocampal long-term
depression, which enhances LTP at neighboring sites
Connection: LTP, con’t
 Glutamate activation of NMDA receptor produces
LTP

These receptors are both transmitter and voltage gated; when
both conditions are met, Mg is ejected and Ca can enter the cell
 Maintenance of LTP may lie in non-NMDA receptors
(such as AMPA receptors)
 Unclear if LTP is due to pre or post-synaptic changes
Connection: LTP, con’t
 5 properties to make LTP a strong model of memory:
1.
2.
3.
4.
5.
Prominent feature of the hippocampus (though it also
occurs elsewhere such as the visual cortex)
Develops rapidly (within 1 min of stimulus)
Long-lasting (hours after a single stimulus, or for >weeks if
given “reminder” stimuli)
Strong specificity: Only those synapses activated during the
stimulation train are potentiated (other neighboring
synapses, even on the same neurons, are not altered)
Associative: potentiation occurs best when multiple inputs
are stimulated simultaneously during the tetanus
Compartmentalization
Memory
Declarative (explicit)
Facts
Events
Non-declarative (implicit)
Skills and
Habits
Priming
Simple Classical
Conditioning
Medial temporal lobe
Diencephalon
Emotional
Responses
Skeletal
Musculature
Striatum
Amygdala
Nonassociative
Learning
Cerebellum
Neocortex
Reflex
pathways
Short-Term Memory
 Sensory Memory: milliseconds to seconds
 Short-term/Immediate Memory: seconds to minutes
 Reason for forgetting: decay v. interference (usually
interference)
 Order matters: serial pattern effect



Primacy and Recency effects – we are better at remembering
things in the beginning and ending of a list
Primacy: transfer occurs from short to long-term memory
through repitition
Recency: retention in short-term memory
Short-Term Memory Capacity
 Regardless of the information in the items, the number of
items retained is around 7*
 Sensory Memory is different!
 Memory savants “memorists” remember by various
methods, some exploiting information in packets, others
using visual pictures or stories
*Originally a study by Miller in the 1950’s, then repeated by him in 1994
Short-term Storage v. Level of Processing
Sensory Inputs  Sensory Register  Short-term
Storage  Long-term storage
Rehearsal
Attention
 At any stage, information can be lost due to decay or
interference, or both
 Craik and Lochkart (1972): level of processing
matters
Working Memory
 Baddeley et al proposed the first variant of working
memory – information that can be acted on and
processed
 Somehow, this will lead to long-term memory if
retained
 Pts with amnesia help explain how this works
 Shallice and Warrington – pt w/ L perisylvian damaged
reduced digit span to 2, but could make long-term memories
Animal Models of Memory:
Morris water maze task
Amnesia and Human Memory
 Medial Temporal Lobe – pt H.M. and R.B.
 Mainly anterograde amnesia, but some retrograde amnesia
 Mamillary bodies – Korsakoff’s Syndrome
 Anterograde and retrograde amnesia a/w alcoholism
 Learning in amnesia – are episodic, semantic, and
procedural information different?
Questions?
 Next time: long-term memory,
compartmentalization, and neuroimaging and
memory!