A glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons.
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.
National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, Maryland, USA.
Jia
J
Qi
National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, Maryland, USA.
Shiliang
S
Zhang
National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, Maryland, USA.
Hui-Ling
HL
Wang
National Institute on Drug Abuse, Electrophysiology Research Section, National Institutes of Health, Baltimore, Maryland, USA.
Huikun
H
Wang
National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, Maryland, USA.
Jose
J
de Jesus Aceves Buendia
National Institute on Drug Abuse, Electrophysiology Research Section, National Institutes of Health, Baltimore, Maryland, USA.
Alexander F
AF
Hoffman
National Institute on Drug Abuse, Electrophysiology Research Section, National Institutes of Health, Baltimore, Maryland, USA.
Carl R
CR
Lupica
Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Rebecca P
RP
Seal
National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, Maryland, USA.
Marisela
M
Morales
D026922:Amino Acid Transport Systems, Acidic / Q000502:physiology; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D059290:Dopaminergic Neurons / Q000502:physiology*; D065847:Dorsal Raphe Nucleus / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology*; D062308:Optogenetics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D017557:Ventral Tegmental Area / Q000502:physiology*; D050496:Vesicular Glutamate Transport Proteins / Q000502:physiology
D026922:Amino Acid Transport Systems, Acidic; D050496:Vesicular Glutamate Transport Proteins; C482103:Slc17a8 protein, rat; C504941:Slc17a8 protein, mouse