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Cell Rep. 2019 Jan 29;26(5):1128-1142.e7. doi: 10.1016/j.celrep.2019.01.014.

Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons.

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National Institute on Drug Abuse, Neuronal Networks Section, NIH, Baltimore, MD, USA.
National Institute on Drug Abuse, Electron Microscopy Core, NIH, Baltimore, MD, USA.
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA.
National Institute on Drug Abuse, Neuronal Networks Section, NIH, Baltimore, MD, USA. Electronic address:


Dorsal 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.


VGluT3; dorsal raphe nucleus; reward; serotonin; ventral tegmental area

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