drug-driven ampa receptor redistribution mimicked by selective dopamine neuron stimulationdrug-driven ampa受体选择性刺激多巴胺神经元再分配模仿.pdfVIP

Drug-Driven AMPA Receptor Redistribution Mimicked by Selective Dopamine Neuron Stimulation 1 1 1 ` 1 1 Matthew T. C. Brown , Camilla Bellone , Manuel Mameli , Gwenael Labouebe , Christina Bocklisch , ´ ´ 1 1 ´ 2 3 ¨ 1,4 Benedicte Balland , Lionel Dahan , Rafael Lujan , Karl Deisseroth , Christian Luscher * 1 Department of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, Switzerland, 2 Departamento de Ciencias Medicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain, 3 Departments of Bioengineering and Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, United States of America, 4 Clinic of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland Abstract Background: Addictive drugs have in common that they cause surges in dopamine (DA) concentration in the mesolimbic reward system and elicit synaptic plasticity in DA neurons of the ventral tegmental area (VTA). Cocaine for example drives insertion of GluA2-lacking AMPA receptors (AMPARs) at glutamatergic synapes in DA neurons. However it remains elusive which molecular target of cocaine drives such AMPAR redistribution and whether other addictive drugs (morphine and nicotine) cause similar changes through their effects on the mesolimbic DA system. Methodology / Principal Findings: We used in vitro electrophysiological techniques in wild-type and transgenic mice to observe the modulation of excitatory inputs onto DA neurons by addictive drugs. To observe AMPAR redistribution, post- embedding imm