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

Martine Migaud, Paul Charlesworth, Maureen Dempster, Lorna C. Webster, Ayako M. Watabe, Michael Makhinson, Yong He, Mark F. Ramsay, Richard G.M. Morris, John Morrison, Thomas J. O'Dell, Seth G.N. Grant

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886 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)433-439
Number of pages7
JournalNature
Volume396
Issue number6710
DOIs
StatePublished - Dec 3 1998
Externally publishedYes

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    Migaud, M., Charlesworth, P., Dempster, M., Webster, L. C., Watabe, A. M., Makhinson, M., He, Y., Ramsay, M. F., Morris, R. G. M., Morrison, J., O'Dell, T. J., & Grant, S. G. N. (1998). Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature, 396(6710), 433-439. https://doi.org/10.1038/24790