Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice

Nature. 1995 Jun 1;375(6530):400-4. doi: 10.1038/375400a0.


Long-term potentiation (LTP) is an enhancement of synaptic strength that can be produced by pairing of presynaptic activity with postsynaptic depolarization. LTP in the hippocampus has been extensively studied as a cellular model of learning and memory, but the nature of the underlying synaptic modification remains elusive, partly because our knowledge of central synapses is still limited. One proposal is that the modification is postsynaptic, and that synapses expressing only NMDA (N-methyl-D-aspartate) receptors before potentiation are induced by LTP to express functional AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) receptors. Here we report that a high proportion of synapses in hippocampal area CA1 transmit with NMDA receptors but not AMPA receptors, making these synapses effectively non-functional at normal resting potentials. These silent synapses acquire AMPA-type responses following LTP induction. Our findings challenge the view that LTP in CA1 involves a presynaptic modification, and suggest instead a simple postsynaptic mechanism for both induction and expression of LTP.

Publication types

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

MeSH terms

  • Animals
  • Electric Stimulation
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Long-Term Potentiation / physiology*
  • Neurotransmitter Agents / metabolism
  • Patch-Clamp Techniques
  • Rats
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / physiology*


  • Neurotransmitter Agents
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate