Article

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

  • Nature Communications 5, Article number: 5390 (2014)
  • doi:10.1038/ncomms6390
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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.

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Acknowledgements

The Intramural Research Program of the National Institute on Drug Abuse (IRP/NIDA/NIH) supported this work. We thank Eduardo D. Gigante for technical assistance. We thank Roy A. Wise and M. Flavia Barbano for critical reading and helpful discussions.

Author information

Author notes

    • Jia Qi
    • , Shiliang Zhang
    •  & Hui-Ling Wang

    These authors contributed equally to this work

Affiliations

  1. National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, Maryland, USA

    • Jia Qi
    • , Shiliang Zhang
    • , Hui-Ling Wang
    • , Jose de Jesus Aceves Buendia
    •  & Marisela Morales
  2. National Institute on Drug Abuse, Electrophysiology Research Section, National Institutes of Health, Baltimore, Maryland, USA

    • Huikun Wang
    • , Alexander F. Hoffman
    •  & Carl R. Lupica
  3. Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    • Rebecca P. Seal

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Contributions

M.M., J.Q., S.Z. and H-L.W. designed the experiments. J.Q., S.Z., H-L.W., H.W. and J.d.J.A.B. performed the experiments. M.M., C.R.L., J.Q., S.Z., H-L.W., J.d.J.A.B., H.W. and A.F.H. analysed the data. R.P.S developed and provided the VGluT3::Cre mice. M.M. wrote the paper with the contribution of all co-authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Marisela Morales.

Supplementary information

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    Supplementary Information

    Supplementary Figures 1-11, Supplementary Table 1.

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