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

Specific patterns of neuronal firing induce changes in synaptic strength th at may contribute to learning and memory. If the postsynaptic NMDA (N-methy l-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 p ostsynaptic density-95 (PSD-95), which may regulate the localization of and /or signalling by the receptor, In mutant mice lacking PSD-95, the frequenc y function of NMDA-dependent LTP and LTD is shifted to produce strikingly e nhanced LTP at different frequencies of synaptic stimulation. In keeping wi th neural-network models that Incorporate bidirectional learning rules, thi s frequency shift is accompanied by severely impaired spatial learning. Syn aptic NMDA-receptor currents, subunit expression, localization and synaptic morphology are all unaffected in the mutant mice. PSD-95 thus appears to b e important in coupling the NMDA receptor to pathways that control bidirect ional synaptic plasticity and learning.