清华本科课件《神经病学》Molecular and cellular mechanisms of learning and memory 723507909.pdfVIP

Molecular and cellular mechanisms of learning and memory Guosong Liu Tsinghua How does neural system store information? Molecular mechanisms of memory process Encoding Consolidation Storage Events Working memory Long-term memory Retrieval Hebbs rule Excitatory synapses that successfully stimulate a postsynaptic neuron or are active when the postsynaptic neuron is depolarized are selectively stabilized (Hebb, 1949). The rodent hippocampus Long-term potentiation (LTP) of Schaffer collateral-CA1 synapses LTP of Schaffer collateral-CA1 synapses LTP of Schaffer collateral-CA1 synapses Long-term synaptic depression (LTD) in the hippocampus Molecular mechanisms of LTP Pairing presynaptic and postsynaptic activity causes LTP Activation of NMDA receptor is required for induction of LTP NMDA receptor gating (Danysz, SciTopics) The NMDA receptor channel can open only during depolarization Signaling mechanisms underlying LTP How to prove that NMDAR signaling is critical for memory function? . Lack of the NMDAR1 Subunit in the CA1 Region in CA1-KO Mice In situ hybridization of NMDAR1 mRNA from wt (A) and CA1-KO (B) brains. ctx, cortex; DG, dentate gyrus. The Performance of CA1-KO Mice in the Water Maze CA1-KO mice are slower in learning the hidden-platform version of the Morris water maze. The graph represents the escape latencies of mice trained to find a hidden platform in a water maze by using the distal cues surrounding it. The CA1-KO mice (closed circles, n =11) display a longer latency in every block (four trials per day) than the cont