Hippocampus and Memory I Case of H M

Hippocampus and Memory I. Case of H. M. - Multiple forms of memory - Memory consolidation II. Neural Basis of Memory - Hebbian synapse - Long-term potentiation - NMDA receptor

Hippocampus

Hippocampus: Two key findings 1. Human: anterograde and retrograde amnesia in H. M. -> Declarative memory theory 2. Rodent: place cells -> Cognitive map theory

Other proposed functions of the hippocampus Emotion (Papez, 1937; Isaacson, 1974) Predictive comparator (Gray, 1982) Configural association (Sutherland & Rudy, 1989) Working memory (Olton, 1976) Context (Hirsh, 1974) Spanning temporal discontiguity (Rawlins, 1985) Recognition of novelty (Gaffan, 1972) Sequence memory (Levy, 1989)

I. Case of H. M.

Anterograde vs. retrograde amnesia Retrograde amnesia Anterograde amnesia Temporal lobectomy H. M. : Almost complete anterograde amnesia following bilateral temporal lobectomy

Multiple forms of memory Mirror drawing and Tower of Hanoi tasks

Taxonomy of long-term memory Long-term memory Declarative memory (Explicit, Knowing what) Episodic memory (remembering events) Semantic memory (knowing facts) Procedural memory (Implicit, Knowing how) Skills & habits Simple Nonassociative classical learning conditioning Priming Neocortex Reflex pathways Hippocampus Parahippocampal region Diencephalon Striatum Cerebellum (musculature) Amygdala (emotional response)

Nonassociative learning: Habituation

Classical (Pavlovian) conditioning Operant (Instrumental) conditioning

Demonstration: Word Priming

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DEFEND DEFACE DEFEAT DEFINE DEFECT DEFROST ETC.

Taxonomy of long-term memory Long-term memory Declarative memory (Explicit, Knowing what) Episodic memory (remembering events) Semantic memory (knowing facts) Procedural memory (Implicit, Knowing how) Skills & habits Simple Nonassociative classical learning conditioning Priming Neocortex Reflex pathways Hippocampus Parahippocampal region Diencephalon Striatum Cerebellum (musculature) Amygdala (emotional response)

Memory Consolidation Anterograde vs. retrograde amnesia Retrograde amnesia Anterograde amnesia Temporal lobectomy H. M. : Graded retrograde amnesia following bilateral temporal lobectomy

Head trauma and amnesia

Retrograde amnesia in animal studies

Models of Memory System Sensory input Intermediate memory Long-term memory Sensory input Intermediate memory over time Long-term memory

Alzheimer’s disease -Hippocampal formation(특히 entorhinal cortex)이 초기에 손상 -초기에는 새로운 기억의 encoding에 문제. 오래된 기억은 정상. Alzheimer’s Disease Normal

II. Neural basis of memory History: 물질 vs. 회로

Declarative memory (associative memory) (content addressable memory) Hebbian synapse Long-term potentiation NMDA receptor

History: two traditional views in memory research 1) Chain of reactions 2) Flashbulb memory (Insight learning)

Hebbian synapse Reverberation Hebbian synapse

Pattern completion based on Hebbian synapse

Pattern completion (content addressable memory) (associative memory)

Recurrent collaterals in the cortex

Experimental evidence for functional assembly formation

Declarative memory (associative memory) (content addressable memory) Hebbian synapse Long-term potentiation NMDA receptor

Long-term potentiation (LTP)

LTP represents Hebbian synapse

Declarative memory (associative memory) (content addressable memory) Hebbian synapse Long-term potentiation NMDA receptor

LTP requires calcium entry through NMDA receptor

Active dendrite (back-propagating action potential)

What change is responsible for synaptic weight enhancement? LTP expression hypotheses 4 1 2 3

LTP & AMPA receptor trafficking Gary Lynch and Michell Baudry THE BIOCHEMISTRY OF MEMORY: A NEW AND SPECIFIC HYPOTHESIS. Science. 1984, 224(4653): 1057 -63. Robert Malinow and Robert C. Malenka AMPA RECEPTOR TRAFFICKING AND SYNAPTIC PLASTICITY Annu. Rev. Neurosci. 2002, 25: 103– 26

Is LTP the neural basis of memory? Morris water maze: declarative memory task

NMDA receptor mutant mice are impaired in water maze task

Multiple forms of memory Short-term vs. long-term memory 2397461 3987469283756 Working vs. reference memory Declarative vs. procedural memory Associative vs. non-associative memory

Delayed response task & Delay cell