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Resilience to chronic stress is mediated by noradrenergic regulation of dopamine neurons

Nature Neuroscience volume 19, pages 560563 (2016) | Download Citation

Abstract

Dopamine (DA) neurons in the ventral tegmental area (VTA) help mediate stress susceptibility and resilience. However, upstream mechanisms controlling these neurons remain unknown. Noradrenergic (NE) neurons in the locus coeruleus, implicated in the pathophysiology of depression, have direct connections within the VTA. Here we demonstrate that NE neurons regulate vulnerability to social defeat through inhibitory control of VTA DA neurons.

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Acknowledgements

We thank E. Vigneault and M.E. Desaulniers for care and maintenance of the mouse colonies. B.G. is supported by a Canadian Research Chair in the Neurobiology of Mental Disorders. E.I. is supported by a postdoctoral grant from the Fonds de Recherche du Québec - Santé. This work was supported by the Canada Research Chairs program, the Graham Boeckh Foundation for Schizophrenia Research and the Natural and Engineering Research Council of Canada (RGPIN 385732-2012) to B.G.

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Author notes

    • Elsa Isingrini
    •  & Léa Perret

    These authors contributed equally to this work.

Affiliations

  1. Department of Psychiatry, Douglas Mental Health Research Center, McGill University, Montreal, Quebec, Canada.

    • Elsa Isingrini
    • , Léa Perret
    • , Quentin Rainer
    • , Bénédicte Amilhon
    • , Elisa Guma
    • , Arnaud Tanti
    • , Garance Martin
    • , Jennifer Robinson
    • , Luc Moquin
    • , Fabio Marti
    • , Naguib Mechawar
    • , Sylvain Williams
    • , Alain Gratton
    •  & Bruno Giros
  2. Sorbonne Universités, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, Université Pierre et Marie Curie, Paris, France.

    • Garance Martin
    • , Fabio Marti
    •  & Bruno Giros

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Contributions

The studies were conceived and designed by B.G. and E.I. Experiments were performed by E.I. and L.P. with contributions from Q.R. for in vivo optogenetic experiments; Q.R. and F.M. for in vivo electrophysiological recording; E.G., G.M. and J.R. for surgeries; A.G. and L.M. for neurochemical analysis; A.T. and N.M. for the histology; and B.A. and S.W. for patch-clamp recording. The paper was written by B.G., E.I. and L.P., and was edited by the other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Bruno Giros.

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DOI

https://doi.org/10.1038/nn.4245

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