MARISSA DI GIOVINE, PGY5DR. RAPIN’S SEMINAR SERIES

FEBRUARY 2013

The Neuroscience of Memory

Outline of Presentation

Definition of memoryClinical Case – H.M. and how he changed

memoryApproach to memoryCellular level of memoryShort-term memoryLearning 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/memoryNon-associative learningKandel 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.Prominent feature of the hippocampus (though it also occurs elsewhere such as the visual cortex)

2.Develops rapidly (within 1 min of stimulus)3.Long-lasting (hours after a single stimulus, or for

>weeks if given “reminder” stimuli)4.Strong specificity: Only those synapses activated

during the stimulation train are potentiated (other neighboring synapses, even on the same neurons, are not altered)

5.Associative: potentiation occurs best when multiple inputs are stimulated simultaneously during the tetanus

Compartmentalization

Memory

Declarative (explicit)

Facts Events

Non-declarative (implicit)

Skills and PrimingHabits

Simple Classical Nonassociative Conditioning Learning

Emotional SkeletalResponses Musculature

Medial temporal lobeDiencephalon

Striatum Neocorte

xAmygdala

Cerebellum

Reflex pathways

Short-Term Memory

Sensory Memory: milliseconds to secondsShort-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

At any stage, information can be lost due to decay or interference, or both

Craik and Lochkart (1972): level of processing matters

AttentionRehearsal

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!