Dynamic Interactions Mediated by Nonredundant Signaling Mechanisms Couple Circadian Clock Neurons

Interactions among suprachiasmatic nucleus (SCN) neurons are required for robust circadian rhythms entrained to local time. To investigate these signaling mechanisms, we developed a functional coupling assay that uniquely captures the dynamic process by which SCN neurons interact. As a population, SCN neurons typically display synchronized rhythms with similar peak times, but will peak 6-12 hr apart after in vivo exposure to long days. Once they are removed from these conditions, SCN neurons resynchronize through a phase-dependent coupling process mediated by both vasoactive intestinal polypeptide (VIP) and GABAA signaling. Notably, GABAA signaling contributes to coupling when the SCN network is in an antiphase configuration, but opposes synchrony under steady-state conditions. Further, VIP acts together with GABAA signaling to couple the network in an antiphase configuration, but promotes synchrony under steady-state conditions by counteracting the actions of GABAA signaling. Thus, SCN neurons interact through nonredundant coupling mechanisms influenced by the state of the network. •Long day lengths reorganize the mammalian circadian pacemaker•Pacemaker neurons synchronize by shifting one another earlier or later•Coupling is mediated by intercellular communication involving both VIP and GABA•SCN factors interact cooperatively or antagonistically depending on the network state Brain function depends on the synchronized activity of neurons organized into networks. The suprachiasmatic nucleus (SCN) is a neural network that programs daily rhythms. Evans et al. show that the SCN network is plastic in both its organization and intercellular signaling mechanisms.