Heterogeneity between VIP and GRP neurons underlies AVP receptor signaling in the mouse suprachiasmatic nucleus

Understanding the network topology of a cluster of diverse neurons acting in concert requires a detailed expression map of ligand-receptor pairs involved in cell-cell communication. The neuropeptide arginine vasopressin (AVP) and signaling mediated by its cognate receptor V1a have been implicated in dorsal-to-ventral regional communication in the suprachiasmatic nucleus (SCN), a cluster of neurons that acts in concert to generate daily rhythms in behavior and physiology. Here, we show that among vasoactive intestinal peptide (VIP)-ergic neurons in the ventral SCN only a small subpopulation expresses V1a, and we demonstrate the requirement of V1a in these VIP neurons for maintaining the robustness of the circadian clock using a jet-lag paradigm. Notably, we found that V1a expression appears to be minimal in the other major ventral neuronal population expressing gastrin-releasing peptide (GRP). The identified heterogeneity between VIP and GRP neurons, and among VIP neurons, provides a basic map for understanding the cryptic network structure from dorsal AVP neurons to receiver ventral SCN.