Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors

Romain Durand De Cuttoli; Sarah Mondoloni; Fabio Marti; Damien Lemoine; Claire Nguyen; Jérémie Naudé; Thibaut D’izarny-Gargas; Stéphanie Pons; Uwe Maskos; Dirk Trauner; Richard H. Kramer; Philippe Faure; Alexandre Mourot

doi:10.7554/eLife.37487

Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors

Romain Durand De Cuttoli, Sarah Mondoloni, Fabio Marti, Damien Lemoine, Claire Nguyen, Jérémie Naudé, Thibaut D’izarny-Gargas, Stéphanie Pons, Uwe Maskos, Dirk Trauner, Richard H. Kramer, Philippe Faure, Alexandre Mourot

Chemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	e37487
Journal	eLife
Volume	7
DOIs	https://doi.org/10.7554/eLife.37487
State	Published - Sep 2018

ASJC Scopus subject areas

Neuroscience(all)
Immunology and Microbiology(all)
Biochemistry, Genetics and Molecular Biology(all)

Access to Document

10.7554/eLife.37487

Fingerprint Dive into the research topics of 'Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors'. Together they form a unique fingerprint.

Cite this

Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors. / Cuttoli, Romain Durand De; Mondoloni, Sarah; Marti, Fabio; Lemoine, Damien; Nguyen, Claire; Naudé, Jérémie; D’izarny-Gargas, Thibaut; Pons, Stéphanie; Maskos, Uwe; Trauner, Dirk; Kramer, Richard H.; Faure, Philippe; Mourot, Alexandre.

In: eLife, Vol. 7, e37487, 09.2018.

Research output: Contribution to journal › Article › peer-review

Cuttoli, Romain Durand De ; Mondoloni, Sarah ; Marti, Fabio ; Lemoine, Damien ; Nguyen, Claire ; Naudé, Jérémie ; D’izarny-Gargas, Thibaut ; Pons, Stéphanie ; Maskos, Uwe ; Trauner, Dirk ; Kramer, Richard H. ; Faure, Philippe ; Mourot, Alexandre. / Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors. In: eLife. 2018 ; Vol. 7.

@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 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.",

year = "2018",

month = sep,

doi = "10.7554/eLife.37487",

language = "English (US)",

volume = "7",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors

AU - Cuttoli, Romain Durand De

AU - Mondoloni, Sarah

AU - Marti, Fabio

AU - Lemoine, Damien

AU - Nguyen, Claire

AU - Naudé, Jérémie

AU - D’izarny-Gargas, Thibaut

AU - Pons, Stéphanie

AU - Maskos, Uwe

AU - Trauner, Dirk

AU - Kramer, Richard H.

AU - Faure, Philippe

AU - Mourot, Alexandre

N1 - 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 Médicale (Équipe FRM DEQ2013326488 to P.F.), by the French National Cancer Institute Grant TABAC-16–022 (to P.F.) by the Fédération de la Recherche pour le Cerveau (FRC Rotary Espoir en tête 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 Pensée program of the Région 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 École des Neurosciences de Paris Ile-de-France RTRA network. P.F. is member of LabEx BioPsy and of DHU Pepsy.

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85058369358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058369358&partnerID=8YFLogxK

U2 - 10.7554/eLife.37487

DO - 10.7554/eLife.37487

M3 - Article

C2 - 30176987

AN - SCOPUS:85058369358

VL - 7

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e37487

ER -