Contributors: Laboratoire Plasticité du Cerveau Brain Plasticity (UMR 8249) (PdC); Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Centre National de la Recherche Scientifique (CNRS); Neuroscience Paris Seine (NPS); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB); Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM); Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC); Institut Pasteur Paris (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Institut de la Vision; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); This work was supported by Centre national de la recherche scientifique (CNRS; UMR 8246), Institut national de la santé et de la recherche médicale (Inserm; U1130), Fondation pour la recherche médicale (FRM; DEQ2013326488 to P.F., FDT201904008060 to S.M., ECO201806006688 to J.J., and SPF202005011922 to C.S.), French National Cancer Institute grants TABAC-16-022 and TABAC-19-020 (to P.F.), French state funds managed by Agence Nationale de la Recherche (ANR-16 Nicostress to P.F., ANR-19 Vampire to F.M.), and LabEx Bio-Psy (to P.F. and a doctoral fellowship to C.N.). L.M.R. was supported by a National Institute on Drug Abuse (NIDA)-Inserm Postdoctoral Drug Abuse Research Fellowship. P.F. and U.M. are members of LabEx Bio-Psy.; ANR-16-CE16-0020,nicostress,Réseaux neuronaux sous-tendant l'intéraction entre stress et nicotine dans le cadre des troubles psychiatriques(2016); ANR-19-CE16-0001,VAmPiRe,Effets opposés de la nicotine sur des neurones dopaminergiques distincts : un rôle spécifique de la voie VTA-Amygdala dans le renforcement(2019); ANR-11-LABX-0035,BIOPSY,Laboratoire de Psychiatrie Biologique(2011)
نبذة مختصرة : International audience ; Nicotine stimulates dopamine (DA) neurons of the ventral tegmental area (VTA) to establish and maintain reinforcement. Nicotine also induces anxiety through an as yet unknown circuitry. We found that nicotine injection drives opposite functional responses of two distinct populations of VTA DA neurons with anatomically segregated projections: it activates neurons that project to the nucleus accumbens (NAc), whereas it inhibits neurons that project to the amygdala nuclei (Amg). We further show that nicotine mediates anxiety-like behavior by acting on β2-subunit-containing nicotinic acetylcholine receptors of the VTA. Finally, using optogenetics, we bidirectionally manipulate the VTA-NAc and VTA-Amg pathways to dissociate their contributions to anxiety-like behavior. We show that inhibition of VTA-Amg DA neurons mediates anxiety-like behavior, while their activation prevents the anxiogenic effects of nicotine. These distinct subpopulations of VTA DA neurons with opposite responses to nicotine may differentially drive the anxiogenic and the reinforcing effects of nicotine.
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