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NMDA receptor expression changes on ventral tegmental (VTA) dopamine neurons after acute cocaine exposure

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Defense Thèse de doctorat : Univ. Genève et Lausanne, 2013 - Neur. 110 - 2013/06/20
Abstract Drug-evoked synaptic plasticity in the mesolimbic dopamine system reorganizes neural circuits that may lead to addictive compulsive behavior. The first cocaine exposure potentiates AMPAR excitatory postsynaptic currents (EPSCs) onto DA neurons of the VTA, but reduces the amplitude of NMDAR-EPSCs. While the plasticity of AMPA transmission is expressed by insertion of calcium (Ca2+)-permeable GluA2-lacking receptors, little is known about the expression mechanism for the altered NMDAR transmission. Combining ex vivo patch clamp recordings, mouse genetics and subcellular Ca2+ imaging, we observe that cocaine drives the insertion of NMDARs that are quasi Ca2+-impermeable and contain GluN3A and GluN2B subunits. These GluN3A-containing NMDARs appear necessary for the expression of cocaine-evoked plasticity of AMPARs. We identify an mGluR1 dependent mechanism to remove these "non-canonical" NMDARs that requires Homer/Shank interaction and protein synthesis. Our data provide insight into the early cocaine-driven reorganization of glutamatergic transmission onto DA neurons and offers GluN3A-containing NMDARs as a new target in drug addiction.
Keywords NMDA receptorMGluR1VTADopamineCocaineSynaptyc plasticity
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URN: urn:nbn:ch:unige-290442
Note Thèse en Neurosciences des universités de Genève et de Lausanne
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YUAN, Tifei. NMDA receptor expression changes on ventral tegmental (VTA) dopamine neurons after acute cocaine exposure. Université de Genève. Thèse, 2013. https://archive-ouverte.unige.ch/unige:29044

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Deposited on : 2013-08-05

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