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

eLife | 2018

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.

Pubmed ID: 30176987 RIS Download

Associated grants

  • Agency: Agence Nationale de la Recherche, International
    Id: ANR-JCJC
  • Agency: Fondation pour la Recherche Médicale, International
    Id: PhD fellowship FDT20170437427
  • Agency: NIH HHS, United States
    Id: U01-NS090527
  • Agency: Fondation de France, International
    Id: Fondation Medisite fundamental research prize
  • Agency: Labex, International
    Id: Bio-Psy post-doctoral fellowship
  • Agency: Brain and Behavior Research Foundation, International
    Id: NARSAD Young Investigator Grant
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS100911
  • Agency: Fédération pour la Recherche sur le Cerveau, International
    Id: Rotary Espoir en tête 2012
  • Agency: Fondation pour la Recherche Médicale, International
    Id: Equipe FRM DEQ2013326488
  • Agency: Institut National Du Cancer, International
    Id: TABAC-16-022
  • Agency: NINDS NIH HHS, United States
    Id: U01 NS090527
  • Agency: DIM Cerveau Pensée, International
    Id: PhD fellowship
  • Agency: NIH HHS, United States
    Id: R01-NS100911
  • Agency: NEI NIH HHS, United States
    Id: P30 EY003176

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