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Scientific article
English

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

Published inEuropean journal of neuroscience, vol. 21, no. 5, p. 1280-1288
Publication date2005
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.

Keywords
  • 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/radiation effects
  • Indoles/pharmacology
  • Long-Term Synaptic Depression/drug effects/ physiology/radiation effects
  • Maleimides/pharmacology
  • Neural Inhibition/drug effects
  • Neurons/drug effects/ physiology/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/radiation effects
  • Ventral Tegmental Area/cytology/ physiology
Citation (ISO format)
BELLONE, Camilla, LUESCHER, Christian. mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors. In: European journal of neuroscience, 2005, vol. 21, n° 5, p. 1280–1288. doi: 10.1111/j.1460-9568.2005.03979.x
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ISSN of the journal0953-816X
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