@article{9b670f4e9e534a1a813d59db5db16e33,
title = "Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors",
abstract = "Dopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet the temporal dynamic range and mechanism of action of acetylcholine (ACh) on the modulation of VTA circuits and reward-related behaviors are not known. Here, we used a chemical-genetic approach for rapid and precise optical manipulation of nicotinic neurotransmission in VTA neurons in living mice. We provide direct evidence that the ACh tone fine-tunes the firing properties of VTA DA neurons through β2-containing (β2*) nicotinic ACh receptors (nAChRs). Furthermore, locally photo-antagonizing these receptors in the VTA was sufficient to reversibly switch nicotine reinforcement on and off. By enabling control of nicotinic transmission in targeted brain circuits, this technology will help unravel the various physiological functions of nAChRs and may assist in the design of novel therapies relevant to neuropsychiatric disorders.",
author = "Cuttoli, {Romain Durand De} and Sarah Mondoloni and Fabio Marti and Damien Lemoine and Claire Nguyen and J{\'e}r{\'e}mie Naud{\'e} and Thibaut D{\textquoteright}izarny-Gargas and St{\'e}phanie Pons and Uwe Maskos and Dirk Trauner and Kramer, {Richard H.} and Philippe Faure and Alexandre Mourot",
note = "Funding Information: Authors would like to thank Nadine Mouttajagane, Ambre Bonnet and Michael Martin for molecular biology work, and Justine Hadjerci, Steve Didienne and Samir Takillah for their help with electro-physiology and behavior experiments. This work was supported by the Agence Nationale de la Recherche (ANR-JCJC 2014 to A.M.), by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (to A.M.), by the Fondation pour la Recherche M{\'e}dicale ({\'E}quipe FRM DEQ2013326488 to P.F.), by the French National Cancer Institute Grant TABAC-16–022 (to P.F.) by the F{\'e}d{\'e}ration de la Recherche pour le Cerveau (FRC Rotary Espoir en t{\^e}te 2012 to P.F.) and by the Labex Bio-Psy. A.M. was recipient of a fundamental research prize from the Medisite Foundation for Neuroscience. R.D.C. was supported by a Ph.D. fellowship from the DIM Cerveau and Pens{\'e}e program of the R{\'e}gion Ile-de-France, and by a fourth-year Ph.D. fellowship from FRM (FDT20170437427). D.L. was recipient of a Labex Biopsy post-doctoral fellowship. RHK was supported by grants from the NIH (U01-NS090527 and R01-NS100911). P.F. and A.M. laboratory is part of the {\'E}cole des Neurosciences de Paris Ile-de-France RTRA network. P.F. is member of LabEx BioPsy and of DHU Pepsy.Funder Grant reference number Author DIM Cerveau Pens{\'e}e PhD fellowship Romain Durand-de Cuttoli Fondation pour la Recherche M{\'e}dicale PhD fellowship FDT20170437427 Romain Durand-de Cuttoli Labex Bio-Psy post-doctoral fellowship Damien Lemoine National Institutes of Health U01-NS090527 Richard H Kramer Fondation pour la Recherche M{\'e}dicale Equipe FRM DEQ2013326488 Philippe Faure Institut National Du Cancer TABAC-16-022 Philippe Faure F{\'e}d{\'e}ration pour la Recherche sur le Cerveau Rotary Espoir en t{\^e}te 2012 Philippe Faure Brain and Behavior Research Foundation NARSAD Young Investigator Grant Alexandre Mourot Agence Nationale de la Recherche ANR-JCJC Alexandre Mourot Fondation de France Fondation Medisite fundamental research prize Alexandre Mourot National Institutes of Health R01-NS100911 Richard H Kramer The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding Information: Authors would like to thank Nadine Mouttajagane, Ambre Bonnet and Michael Martin for molecular biology work, and Justine Hadjerci, Steve Didienne and Samir Takillah for their help with electrophysiology and behavior experiments. This work was supported by the Agence Nationale de la Recherche (ANR-JCJC 2014 to A.M.), by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (to A.M.), by the Fondation pour la Recherche M{\'e}dicale ({\'E}quipe FRM DEQ2013326488 to P.F.), by the French National Cancer Institute Grant TABAC-16–022 (to P.F.) by the F{\'e}d{\'e}ration de la Recherche pour le Cerveau (FRC Rotary Espoir en t{\^e}te 2012 to P.F.) and by the Labex Bio-Psy. A.M. was recipient of a fundamental research prize from the Medisite Foundation for Neuroscience. R.D.C. was supported by a Ph.D. fellowship from the DIM Cerveau and Pens{\'e}e program of the R{\'e}gion Ile-de-France, and by a fourth-year Ph.D. fellowship from FRM (FDT20170437427). D.L. was recipient of a Labex Biopsy post-doctoral fellowship. RHK was supported by grants from the NIH (U01-NS090527 and R01-NS100911). P.F. and A.M. laboratory is part of the {\'E}cole des Neurosciences de Paris Ile-de-France RTRA network. P.F. is member of LabEx BioPsy and of DHU Pepsy. Publisher Copyright: {\textcopyright} Durand-de Cuttoli et al.",
year = "2018",
month = sep,
doi = "10.7554/eLife.37487",
language = "English (US)",
volume = "7",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}