A NEURONAL RYANODINE RECEPTOR MEDIATES LIGHT-INDUCED PHASE DELAYS OF THE CIRCADIAN CLOCK

Circadian clocks are complex biochemical systems that cycle with a per iod of approximately 24 hours. They integrate temporal information reg arding phasing of the solar cycle, and adjust their phase so as to syn chronize an organism's internal state to the local environmental day a nd night(1,2). Nocturnal light is the dominant regulator of this entra inment. In mammals, information about nocturnal light is transmitted b y glutamate released om retinal projections to the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Clock resetting requi res the activation of ionotropic glutamate receptors, which mediate Ca 2+ influx(3). The response induced by such activation depends on the c lock's temporal state: during early night it delays the clock phase, w hereas in late night the clock phase is advanced. To investigate this differential response, we sought signalling elements that contribute s olely to phase delay. We analysed intracellular calcium-channel ryanod ine receptors, which mediate coupled Ca2+ signalling, Depletion of int racellular Ca2+ stores during early night blocked the effects of gluta mate. Activators of ryanodine receptors induced phase resetting only i n early night; inhibitors selectively blocked delays induced by light and glutamate. These findings implicate the release of intracellular C a2+ through ryanodine receptors in the light-induced phase delay of th e circadian clock restricted to the early night.