Metabotropic Glutamate Receptor Activation Causes a Rapid Redistribution of AMPA Receptors

Neuropharmacology. 2001 Nov;41(6):664-71. doi: 10.1016/s0028-3908(01)00134-4.

Abstract

Electrophysiology, immunostaining and time lapse imaging techniques were employed to study the mechanism of long-term depression (LTD) induced by DHPG, a specific group I metabotropic glutamate receptor (mGluR) agonist. Experiments were performed in primary hippocampal culture or in the CA1 area of acute rat hippocampal slices. In agreement with previous results by others, we show that DHPG (200 microM, 10 min) can induce LTD (DHPG-LTD) in acute slices, in the presence or absence of synaptic inhibition. In addition, in voltage clamp whole cell experiments we find that accompanying the reduction in the evoked excitatory postsynaptic current (EPSC), miniature EPSC amplitude and frequency are reduced. Similar results were obtained in cultured neurons. Immunostaining and time lapse imaging showed a long-lasting loss of AMPA receptors from the membrane surface of cultured neurons after DHPG treatment, which appears to occur in only a subset of the puncta. Further electrophysiological recordings on slices showed that blocking postsynaptic endocytosis by introducing a blocking peptide named D15 in recording pipettes abolished the DHPG-LTD. In conclusion, these data suggest that LTD induced by mGluR activation is due to a rapid removal of AMPA receptors from the postsynaptic membrane.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Depsipeptides*
  • Dynamins
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • GTP Phosphohydrolases / antagonists & inhibitors
  • GTP Phosphohydrolases / metabolism
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • In Vitro Techniques
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Neural Inhibition / drug effects
  • Neurons / drug effects
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Peptides, Cyclic / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism*
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / metabolism*
  • Receptors, Metabotropic Glutamate / physiology
  • Resorcinols / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Depsipeptides
  • Excitatory Amino Acid Agonists
  • Nerve Tissue Proteins
  • Peptides
  • Peptides, Cyclic
  • Receptors, AMPA
  • Receptors, Metabotropic Glutamate
  • Resorcinols
  • jasplakinolide
  • amphiphysin
  • 3,5-dihydroxyphenylglycine
  • GTP Phosphohydrolases
  • Dynamins
  • Glycine