|Title||Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein.|
|Publication Type||Journal Article|
|Year of Publication||1998|
|Authors||Migaud M, Charlesworth P, Dempster M, Webster LC, Watabe AM, Makhinson M, He Y, Ramsay MF, Morris RG, Morrison JH, O'Dell TJ, Grant SG|
|Date Published||1998 Dec 3|
|Keywords||Animals, Electrophysiology, Gene Targeting, Guanylate Kinase, Hippocampus, Intracellular Signaling Peptides and Proteins, Learning, Learning Disorders, Long-Term Potentiation, Maze Learning, Membrane Proteins, Memory, Mice, Mice, Inbred C57BL, Models, Neurological, Mutation, Nerve Tissue Proteins, Receptors, N-Methyl-D-Aspartate, Signal Transduction, Synapses|
Specific patterns of neuronal firing induce changes in synaptic strength that may contribute to learning and memory. If the postsynaptic NMDA (N-methyl-D-aspartate) receptors are blocked, long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission and the learning of spatial information are prevented. The NMDA receptor can bind a protein known as postsynaptic density-95 (PSD-95), which may regulate the localization of and/or signalling by the receptor. In mutant mice lacking PSD-95, the frequency function of NMDA-dependent LTP and LTD is shifted to produce strikingly enhanced LTP at different frequencies of synaptic stimulation. In keeping with neural-network models that incorporate bidirectional learning rules, this frequency shift is accompanied by severely impaired spatial learning. Synaptic NMDA-receptor currents, subunit expression, localization and synaptic morphology are all unaffected in the mutant mice. PSD-95 thus appears to be important in coupling the NMDA receptor to pathways that control bidirectional synaptic plasticity and learning.
|Grant List||/ / Wellcome Trust / United Kingdom|