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A neuropeptide-specific signaling pathway for state-dependent regulation of the mesolimbic dopamine system

par Mollie X. Bernstein, Omar Koita, Marta Trzeciak, Andrew Fan, Daniel T. McAuley, Seung-Woo Jin et Larry S. Zweifel

Publié: 22 juillet 2025
Serveur de preprints: bioRxiv
DOI: 10.1101/2025.07.17.665396

Résumé

Dopamine (DA)-producing neurons of the ventral tegmental area (VTA) regulate consummatory behavior in a state-dependent manner (e.g. when hungry or thirsty). The mechanisms by which and extent to which DA neurons are regulated by these interoceptive signals are poorly understood. Here, we identify transient receptor potential canonical type 6 (TRPC6) channels as selective mediators of neuropeptide receptor-induced calcium signaling in VTA-DA neurons. These channels regulate DA neuron activity and consummatory behavior in a state-dependent manner. We find that TRPC6 channels regulate distinct aspects of neuropeptide-induced calcium signals in DA neurons but make little contribution to calcium dynamics associated with metabotropic neurotransmitter receptor signaling. We further show that TRPC6 channels regulate scalable reward valuation and consummatory behavior in hungry but not thirsty mice. These findings demonstrate that neuropeptide-and neurotransmitter-activated G-protein coupled receptors (GPCRs) regulate cellular calcium dynamics through distinct mechanisms, and that TRPC6 channels are important determinants of how animals respond to different homeostatic demands.

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PREreview Theresa Haunold et al. du club HHMI Transparent and Accountable Peer Review Training Program

Rédigé par Theresa Haunold et Yue Yu du HHMI Transparent and Accountable Peer Review Training Program

Bernstein et al. investigate the role of neuropeptide signaling in ventral tegmental dopamine neurons (VTA_DA), a population implicated in both natural and drug rewards. Using CRISPR-Cas9 mutagenesis in mice, they knock down transient receptor potential canonical type 6 (TRPC6) channels, which are…

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PREreview Yue Yu et al. du club HHMI Transparent and Accountable Peer Review Training Program

Rédigé par Yue Yu et 1 autre auteur du HHMI Transparent and Accountable Peer Review Training Program

Review for “A neuropeptide-specific signaling pathway for state-dependent regulation of the mesolimbic dopamine system”

Yue Yu, Theresa Haunold
…
Lire la PREreview de Yue Yu et d’autres membres du club HHMI Transparent and Accountable Peer Review Training Program