mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors

Eur J Neurosci. 2005 Mar;21(5):1280-8. doi: 10.1111/j.1460-9568.2005.03979.x.

Abstract

Excitatory glutamatergic synapses on dopamine (DA) neurons of the ventral tegmental area (VTA) undergo long-lasting changes during conditioning of natural rewards and in response to drug exposure. It has been suggested that the ensuing context-dependent behavioural changes are associated with an increased efficacy of synaptic afferents determined by the balance of long-term potentiation (LTP) and long-term depression (LTD). However, the molecular nature of the forms of LTP/LTD involved remains elusive. Here, using acute rat brain slices, we describe a form of long-term depression (LTD) that was engaged by synaptic activity or exogenous agonists activating group I metabotropic glutamate receptors (mGluR) and was sensitive to mGluR1 antagonists. Prior to mGluR-LTD, AMPAR mediated excitatory postsynaptic currents (EPSCs) showed strong rectification at positive potentials and were sensitive to Joro spider toxin (JST), a selective blocker of GluR2-lacking AMPARs. After mGluR-LTD, AMPAR EPSCs had linear current-voltage relations and became insensitive to JST. We conclude that activation of mGluR1s triggers a redistribution exchanging native receptors for GluR2 containing AMPARs, ultimately causing LTD that may oppose pathological neuroadaptation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / radiation effects
  • In Vitro Techniques
  • Indoles / pharmacology
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Long-Term Synaptic Depression / radiation effects
  • Maleimides / pharmacology
  • Neural Inhibition / drug effects
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / radiation effects
  • Patch-Clamp Techniques / methods
  • Piperidines / pharmacology
  • Protein Subunits / physiology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / physiology*
  • Spider Venoms / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / radiation effects
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / physiology*

Substances

  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Indoles
  • JSTX spider toxin
  • Maleimides
  • Piperidines
  • Protein Subunits
  • Pyrazoles
  • Receptors, AMPA
  • Spider Venoms
  • AM 251
  • bisindolylmaleimide I