Somatostatin regulates central clock function and circadian responses to light

Abstract

Daily and annual changes in light are processed by central clock circuits that control the timing of behavior and physiology. The suprachiasmatic nucleus (SCN) in the anterior hypothalamus processes daily photic inputs and encodes changes in day length (i.e., photoperiod), but the SCN circuits that regulate circadian and photoperiodic responses to light remain unclear. Somatostatin (SST) expression in the hypothalamus is modulated by photoperiod, but the role of SST in SCN responses to light has not been examined. Our results indicate that SST signaling regulates daily rhythms in behavior and SCN function in a manner influenced by sex. First, we use cell-fate mapping to provide evidence that SST in the SCN is regulated by light via de novo Sst activation. Next, we demonstrate that Sst -/- mice display enhanced circadian responses to light, with increased behavioral plasticity to photoperiod, jetlag, and constant light conditions. Notably, lack of Sst -/- eliminated sex differences in photic responses due to increased plasticity in males, suggesting that SST interacts with clock circuits that process light differently in each sex. Sst -/- mice also displayed an increase in the number of retinorecipient neurons in the SCN core, which express a type of SST receptor capable of resetting the molecular clock. Last, we show that lack of SST signaling modulates central clock function by influencing SCN photoperiodic encoding, network after-effects, and intercellular synchrony in a sex-specific manner. Collectively, these results provide insight into peptide signaling mechanisms that regulate central clock function and its response to light.

An intact pituitary vasopressin system is critical for building a robust circadian clock in the suprachiasmatic nucleus

“…4 F – H ), with PS 50 values comparable to those for CRF-AVP –/– and Pomc-V1b –/– mice. During the preparation of our manuscript, other investigators also reported a similar phenotype of SST –/– mice ( 42 ). Behavioral analyses confirmed that the period length in DD, the phase angle from LD to DD, and the magnitude of phase shift after a short light pulse in SST m/m and SSTR1 –/– mice were essentially identical to those in WT mice ( SI Appendix , Fig.…”

Somatostatin-SSTR3-GSK3 modulates human T-cell responses by inhibiting OXPHOS

“…Under normal physiological conditions, SST is mainly produced in the digestive and nervous systems ( 1 ). with its production in the brain following a circadian rhythm ( 21 ). Aberrant elevations of SST are evident in conditions such as somatostatinoma and inflammatory bowel diseases ( 22 , 23 ).…”