A glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons

Jia Qi, Shiliang Zhang, Hui-Ling Wang, Huikun Wang, Jose de Jesus Aceves Buendia, Alexander F. Hoffman, Carl R. Lupica, Rebecca P. Seal and Marisela Morales ()
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Jia Qi: National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health
Shiliang Zhang: National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health
Hui-Ling Wang: National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health
Huikun Wang: National Institute on Drug Abuse, Electrophysiology Research Section, National Institutes of Health
Jose de Jesus Aceves Buendia: National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health
Alexander F. Hoffman: National Institute on Drug Abuse, Electrophysiology Research Section, National Institutes of Health
Carl R. Lupica: National Institute on Drug Abuse, Electrophysiology Research Section, National Institutes of Health
Rebecca P. Seal: University of Pittsburgh
Marisela Morales: National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Electrical stimulation of the dorsal raphe (DR) and ventral tegmental area (VTA) activates the fibres of the same reward pathway but the phenotype of this pathway and the direction of the reward-relevant fibres have not been determined. Here we report rewarding effects following activation of a DR-originating pathway consisting of vesicular glutamate transporter 3 (VGluT3) containing neurons that form asymmetric synapses onto VTA dopamine neurons that project to nucleus accumbens. Optogenetic VTA activation of this projection elicits AMPA-mediated synaptic excitatory currents in VTA mesoaccumbens dopaminergic neurons and causes dopamine release in nucleus accumbens. Activation also reinforces instrumental behaviour and establishes conditioned place preferences. These findings indicate that the DR–VGluT3 pathway to VTA utilizes glutamate as a neurotransmitter and is a substrate linking the DR—one of the most sensitive reward sites in the brain—to VTA dopaminergic neurons.

Date: 2014
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DOI: 10.1038/ncomms6390

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