Abstract：
:Nociceptin and its receptor are widely distributed throughout the brain in regions associated with reward behavior, yet how and when they act is unknown. Here, we dissected the role of a nociceptin peptide circuit in reward seeking. We generated a prepronociceptin (Pnoc)-Cre mouse line that revealed a unique subpopulation of paranigral ventral tegmental area (pnVTA) neurons enriched in prepronociceptin. Fiber photometry recordings during progressive ratio operant behavior revealed pnVTAPnoc neurons become most active when mice stop seeking natural rewards. Selective pnVTAPnoc neuron ablation, inhibition, and conditional VTA nociceptin receptor (NOPR) deletion increased operant responding, revealing that the pnVTAPnoc nucleus and VTA NOPR signaling are necessary for regulating reward motivation. Additionally, optogenetic and chemogenetic activation of this pnVTAPnoc nucleus caused avoidance and decreased motivation for rewards. These findings provide insight into neuromodulatory circuits that regulate motivated behaviors through identification of a previously unknown neuropeptide-containing pnVTA nucleus that limits motivation for rewards.
journal_name
Celljournal_title
Cellauthors
Parker KE,Pedersen CE,Gomez AM,Spangler SM,Walicki MC,Feng SY,Stewart SL,Otis JM,Al-Hasani R,McCall JG,Sakers K,Bhatti DL,Copits BA,Gereau RW,Jhou T,Kash TJ,Dougherty JD,Stuber GD,Bruchas MRdoi
10.1016/j.cell.2019.06.034subject
Has Abstractpub_date
2019-07-25 00:00:00pages
653-671.e19issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(19)30737-8journal_volume
178pub_type
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