Somatostatin regulates the clock sensitivity to evening light

Entrainment of the internal clock to the light-dark cycle is a fundamental feature of biological rhythms. Here, we show that animals genetically deficient for somatostatin (SST) are unable to respond normally to long photoperiodic conditions, showing a significantly delayed phase of activity. The phase delay is also reproduced in the cognate SSTR1 receptor knockout mice and in mice in which SSTR1 is pharmacologically inhibited. We also provide histological evidence that SST inhibits light-induced activation of SSTR1 cells. Furthermore, chronic administration of CH-275, an SSTR1 agonist, normalizes the phase delay of the circadian clock in SST-deficient mice under long photoperiod. Together, these results provide insights into the inhibitory effect of the SST-SSTR1 system in the regulation of light sensitivity of the central clock in the SCN at dusk.