The daily cycle of light and darkness is the most consistent and pervasive signal from the environment to the central nervous system. Melatonin is the universal dark signal that informs the body of this change in illumination. It also prepares sensory and nervous responses to be ready for the changes in illumination by predicting the onset of darkness or day. It does this my being dually regulated by light and a circadian clock. The clock is itself synchronized to the diurnal cycle by light. Melatonin synthesis is regulated by a multi-enzyme pathway that is under control of the circadian clock and of opsin-like photopigments. Light is the most important entraining agent for the melatonin cycle since it both entrains the circadian clock and acutely suppresses melatonin synthesis. Two cell types, photoreceptors of the retina and pinealocytes of the pineal eye of lower vertebrates are known to synthesize melatonin rhythmically under regulation of an endogenous circadian oscillator and to photoregulate melatonin synthesis using opsin-like photopigments. This proposal puts forth the pineal eye of the chick as a model system in which to identify key elements in this transduction pathway. It takes advantage of the recent identification of the chick pineal eye photopigment (P-opsin) and seeks to identify other elements in the transduction pathway. The pineal eye has several advantages as a model system. The pineal eye's primary function is to transduce diurnal lighting information into a melatonin signal, thus many of the molecules expressed in the pineal will be devoted to this task. It is made up of relatively few cell types, primarily pinealocytes and it is relatively easy to culture. In culture, pinealocytes retain the full range of photoreceptive and circadian functions. The level of melatonin expression is sufficiently robust so as to make its measurement in a real time, flow through culture extremely reliable. Many pharmacological and perturbation type investigations overs the past few years provide the basis for the molecular identification of key transduction elements described in the following pages.
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