1. MARISSA DI GIOVINE, PGY5 DR. RAPIN’S SEMINAR SERIES FEBRUARY 2013 The Neuroscience of Memory

2. 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

3. 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

4. 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

5. 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?

6. Connection The Neuron  Electrotonic Conduction  Action Potential  Synaptic Transmission

7. 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)

8. 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: 1 st /conditioned stimulus = bell, 2 nd /unconditioned stimulus = food; conditioned response = salvation when hearing the bell

9. 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

10. 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

11. 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

12. Compartmentalization Memory Declarative (explicit) Facts Events Non-declarative (implicit) Skills and Priming Habits Simple Classical Nonassociative Conditioning Learning Emotional Skeletal Responses Musculature Medial temporal lobe Diencephalon Striatum Neocortex Amygdala Cerebellum Reflex pathways

13. 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

14. 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

15. 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 Attention Rehearsal

16. 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

17. Animal Models of Memory: Morris water maze task

18. 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?

19. Questions? Next time: long-term memory, compartmentalization, and neuroimaging and memory!