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

M Migaud, Paul Charlesworth, M Dempster, Claire L. Webster, Ayako M Watabe, M Makhinson, Y He, M F Ramsay, R G Morris, J H Morrison, T. J. O'Dell, S G Grant

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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
Pages (from-to)433-9
Number of pages7
Issue number6710
Publication statusPublished - 3 Dec 1998

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Disks Large Homolog 4 Protein
  • Electrophysiology
  • Gene Targeting
  • Guanylate Kinases
  • 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
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.


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