Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons

Neuron. 2000 Feb;25(2):473-80. doi: 10.1016/s0896-6273(00)80909-5.


In humans the hippocampus is required for episodic memory, which extends into the spatial and temporal domains. Work on the rodent hippocampus has shown that NMDA receptor (NMDAR) -mediated plasticity is essential for spatial memory. Here, we have examined whether hippocampal NMDARs are also needed for temporal memory. We applied trace fear conditioning to knockout mice lacking NMDARs only in hippocampal CA1 pyramidal cells. This paradigm requires temporal processing because the conditional and unconditional stimuli are separated by 30 s (trace). We found that knockout mice failed to memorize this association but were indistinguishable from normal animals when the trace was removed. Thus, NMDARs in CA1 are crucial for the formation of memories that associate events across time.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • Conditioning, Psychological / physiology
  • Fear
  • Hippocampus / chemistry
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Male
  • Mental Recall / physiology*
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity / physiology
  • Pyramidal Cells / chemistry
  • Pyramidal Cells / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Time Factors


  • Receptors, N-Methyl-D-Aspartate