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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
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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: 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)
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 Procedural memory (Explicit, Knowing what) (Implicit, Knowing how) Episodic memory Semantic memory Skills & habits Simple Nonassociative Priming (remembering events) (knowing facts) classical learning conditioning Neocortex Reflex pathways Hippocampus Striatum Cerebellum Parahippocampal region (musculature) Diencephalon Amygdala (emotional response)
Classical (Pavlovian) conditioning Operant (Instrumental) conditioning
Demonstration: Word Priming
DEFEND DEFACE DEFEAT DEFINE DEFECT DEFROST ETC.
Taxonomy of long-term memory Long-term memory Declarative memory Procedural memory (Explicit, Knowing what) (Implicit, Knowing how) Episodic memory Semantic memory Skills & habits Simple Nonassociative Priming (remembering events) (knowing facts) classical learning conditioning Neocortex Reflex pathways Hippocampus Striatum Cerebellum Parahippocampal region (musculature) Diencephalon Amygdala (emotional response)
Memory Consolidation Anterograde vs. retrograde amnesia Retrograde amnesia Anterograde amnesia Temporal lobectomy H.M. : Graded retrograde amnesia following bilateral temporal lobectomy
Models of Memory System Sensory input Intermediate memory Long-term memory Sensory input Sensory input Intermediate memory Intermediate memory over time Long-term memory Long-term memory
Why memory consolidation? -Not known. -가설: 모든 정보를 그대로 기억하면 용량문제, 또한 필요없는 기억을 저장하는 효율성 문제가 있음. 이를 피하기 위해 intermediate -> long-term memory system이 발달되었음. -가설: 신경망 연구에 따르면 새로운 정보를 기존 지식체계에 급속히 학습시키면 기존 지식체계가 와해됨. 이를 피하려면 새로운 정보를 서서히 기존 지식체계에 편입해야함. Intermediate memory system은 이를 위해 발달. (꿈은 새로운 정보가 기존지식체계로 전달되는 과정?)
Alzheimer’s disease -Hippocampal formation(특히 entorhinal cortex)이 초기에 손상 -초기에는 새로운 기억의 encoding에 문제. 오래된 기억은 정상. Alzheimer’s Disease Normal
Where is long-term memory stored? -Association cortex에 손상이 있을때, 손상부위에 따라 이미 알고있던 얼굴, 물건, 또는 장소 등에 대한 기억이 손상되는 경우가 보고됨. -Temporal lobe를 전기적으로 자극하면 어떤 사건의 경험과 같은 복잡한 sensation 유발 -> activation of memories? -원숭이 inferotemporal lobe의 뉴런들은 학습에 따라 특정물체에 반응하는 양상이 달라짐 -> indication of memory? -Visual imagery때 visual association cortex가 활성화 됨. -Neocortex도 시냅스 가소성이 보고됨. -이러한 결과를 종합할 때 long-term memory는 association cortex에 저장되는 것으로 보임.
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 (content addressable memory) (associative memory)
Neural network -신경망 연구에 의해 Hebbian synapse가 associative memory를 저장할수 있다고 이론적으로 밝혀짐 (Hopfield, 1984). -이때 신경세포들간의 상호연결이 중요함. -신경계에서는 recurrent collateral에 의해 상호연결됨.
Declarative memory (associative memory) (content addressable memory) Hebbian synapse Long-term potentiation NMDA receptor
Declarative memory (associative memory) (content addressable memory) Hebbian synapse Long-term potentiation 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