Circadian neurons in the paraventricular nucleus entrain and sustain daily rhythms in glucocorticoids

Signals from the central circadian pacemaker, the suprachiasmatic nucleus (SCN), must be decoded to generate daily rhythms in hormone release. Here, we hypothesized that the SCN entrains rhythms in the paraventricular nucleus (PVN) to time the daily release of corticosterone. In vivo recording revealed a critical circuit from SCN vasoactive intestinal peptide (SCN(VIP))-producing neurons to PVN corticotropin-releasing hormone (PVN(CRH))-producing neurons. PVN(CRH) neurons peak in clock gene expression around midday and in calcium activity about three hours later. Loss of the clock gene Bmal1 in CRH neurons results in arrhythmic PVN(CRH) calcium activity and dramatically reduces the amplitude and precision of daily corticosterone release. SCN(VIP) activation reduces (and inactivation increases) corticosterone release and PVN(CRH) calcium activity, and daily SCN(VIP) activation entrains PVN clock gene rhythms by inhibiting PVN(CRH) neurons. We conclude that daily corticosterone release depends on coordinated clock gene and neuronal activity rhythms in both SCN(VIP) and PVN(CRH) neurons.