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Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein.

TitleEnhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein.
Publication TypeJournal Article
Year of Publication1998
AuthorsMigaud 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 Published1998 Dec 3
KeywordsAnimals, 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.

Alternate JournalNature
PubMed ID9853749
Grant List / / Wellcome Trust / United Kingdom