Bidirectional, activity-dependent regulation of glutamate receptors in the adult hippocampus in vivo

Neuron. 2000 Nov;28(2):527-36. doi: 10.1016/s0896-6273(00)00130-6.


Experience-dependent regulation of synaptic strength has been suggested as a physiological mechanism by which memory storage occurs in the brain. Although modifications in postsynaptic glutamate receptor levels have long been hypothesized to be a molecular basis for long-lasting regulation of synaptic strength, direct evidence obtained in the intact brain has been lacking. Here we show that in the adult brain in vivo, synaptic glutamate receptor trafficking is bidirectionally, and reversibly, modified by NMDA receptor-dependent synaptic plasticity and that changes in glutamate receptor protein levels accurately predict changes in synaptic strength. These findings support the idea that memories can be encoded by the precise experience-dependent assignment of glutamate receptors to synapses in the brain.

Publication types

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

MeSH terms

  • Animals
  • Electric Stimulation
  • Electrodes, Implanted
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Hippocampus / metabolism*
  • Long-Term Potentiation / physiology
  • Male
  • Memory / physiology
  • Neural Inhibition / physiology
  • Neuronal Plasticity / physiology
  • Protein Transport / physiology*
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Synaptosomes / metabolism
  • Time


  • Excitatory Amino Acid Antagonists
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • glutamate receptor ionotropic, AMPA 2
  • glutamate receptor ionotropic, AMPA 1