1. Centre for Genome Research, and Centre for Neuroscience, University of Edinburgh, Roger Land Building, West Mains Road, Edinburgh EH9 3JQ, UK
2. Centre for Neuroscience, University of Edinburgh, Roger Land Building, West Mains Road, Edinburgh EH9 3JQ, UK
3. Department of Physiology and The Brain Research Institute, School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
4. Fishberg Research Centre for Neurobiology, Mount Sinai School of Medicine, Box 1065, One Gustave Levy Place, New York, New York 10029-6574, USA

Correspondence to: Seth G. N. Grant^1,2 Correspondence and requests for materials should be addressed to S.G.N.G. (e-mail: Email: seth.grant@ed.ac.uk).

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.

1. Centre for Genome Research, and Centre for Neuroscience, University of Edinburgh, Roger Land Building, West Mains Road, Edinburgh EH9 3JQ, UK
2. Centre for Neuroscience, University of Edinburgh, Roger Land Building, West Mains Road, Edinburgh EH9 3JQ, UK
3. Department of Physiology and The Brain Research Institute, School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
4. Fishberg Research Centre for Neurobiology, Mount Sinai School of Medicine, Box 1065, One Gustave Levy Place, New York, New York 10029-6574, USA

Correspondence to: Seth G. N. Grant^1,2 Correspondence and requests for materials should be addressed to S.G.N.G. (e-mail: Email: seth.grant@ed.ac.uk).