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

eLife, ISSN: 2050-084X, Vol: 7
2018
  • 57
    Citations
  • 0
    Usage
  • 124
    Captures
  • 0
    Mentions
  • 22
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    57
  • Captures
    124
  • Social Media
    22
    • Shares, Likes & Comments
      22
      • Facebook
        22

Article Description

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.

Bibliographic Details

Durand-de Cuttoli, Romain; 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

eLife Sciences Publications, Ltd

Neuroscience; Immunology and Microbiology; Biochemistry, Genetics and Molecular Biology

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