Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons
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AbstractDorsal raphe (DR) serotonin neurons provide a major input to the ventral tegmental area (VTA). Here, we show that DR serotonin transporter (SERT) neurons establish both asymmetric and symmetric synapses on VTA dopamine neurons, but most of these synapses are asymmetric. Moreover, the DR-SERT terminals making asymmetric synapses on VTA dopamine neurons coexpress vesicular glutamate transporter 3 (VGluT3; transporter for accumulation of glutamate for its synaptic release), suggesting the excitatory nature of these synapses. VTA photoactivation of DR-SERT fibers promotes conditioned place preference, elicits excitatory currents on mesoaccumbens dopamine neurons, increases their firing, and evokes dopamine release in nucleus accumbens. These effects are blocked by VTA inactivation of glutamate and serotonin receptors, supporting the idea of glutamate release in VTA from dual DR SERT-VGluT3 inputs. Our findings suggest a path-specific input from DR serotonergic neurons to VTA that promotes reward by the release of glutamate and activation of mesoaccumbens dopamine neurons. Copyright 2019
SponsorsWe thank Dr. Roy Wise for critical reading of the manuscript and Drs. David Barker and Stephan Steidl for advice on behavioral studies. The Intramural Research Program of the National Institute on Drug Abuse (NIDA/NIH) supported this work. J.F.C. was supported by NIDA grants DA022340 and DA042595 . C.A.P. was supported by NIDA grant DA038453 and NIMH grants MH107229 and MH113341 . J.A.G. was supported by NIDA grant DA041303 . Resources for three-dimensional analysis were supported by NS050274 .
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85059866842&doi=10.1016%2fj.celrep.2019.01.014&partnerID=40&md5=509ba0f3f19b2a4ddcebeef976854d07; http://hdl.handle.net/10713/8678