Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein.
Migaud, Martine; Charlesworth, Paul; Dempster, Maureen; Webster, Lorna C.; Watabe, Ayako M.; Makhinson, Michael; He, Yong; Ramsay, Mark F.; Morris, Richard G. M.; Morrison, John H.; O'Dell, Thomas J.; Grant, Seth G. N.
[Article] Nature. 396(6710):433-439, December 3, 1998.

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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.

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