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mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors |
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Published in | European journal of neuroscience. 2005, vol. 21, no. 5, p. 1280-1288 | |
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 | |
Identifiers | PMID: 15813937 | |
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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 https://archive-ouverte.unige.ch/unige:10183 |