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Title

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 AnimalsAnimals, NewbornDose-Response Relationship, RadiationDrug InteractionsElectric Stimulation/methodsEnzyme Inhibitors/pharmacologyExcitatory Amino Acid Agonists/pharmacologyExcitatory Amino Acid Antagonists/pharmacologyExcitatory Postsynaptic Potentials/drug effects/radiation effectsIndoles/pharmacologyLong-Term Synaptic Depression/drug effects/ physiology/radiation effectsMaleimides/pharmacologyNeural Inhibition/drug effectsNeurons/drug effects/ physiology/radiation effectsPatch-Clamp Techniques/methodsPiperidines/pharmacologyProtein Subunits/physiologyPyrazoles/pharmacologyRatsRats, Sprague-DawleyReceptors, AMPA/ physiologySpider Venoms/pharmacologySynaptic Transmission/drug effects/radiation effectsVentral Tegmental Area/cytology/ physiology
Stable URL http://archive-ouverte.unige.ch/unige:10183
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PMID: 15813937
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