Most organisms, including humans, exhibit daily rhythms in their behavior and physiology. In most cases, these rhythms are generated by endogenous processes referred to as circadian oscillators. These oscillators provide temporal structure to an organism's physiological processes. Nearly all functions of the body show significant daily variations including arousal, cognition, learning, memory, motor performance and perception. This temporal variation obviously plays an important role in the body's homeostatic mechanisms and has a major impact on the function of the nervous system. In order to function adaptively, circadian oscillators must be synchronized to the environment and the daily cycle of light and dark is the dominant cue used by organisms, including humans, to synchronize their biological clocks to the environment. In humans, desynchronization results in symptoms of fatigue, gastrointestinal distress, and poor cognitive performance. Thus, a major goal of this research area, and the focus of this grant proposal, is to understand the mechanisms by which light acts to synchronize the circadian oscillator located in the suprachiasmatic nucleus (SCN). Previous work has shown that glutamate is a transmitter that conveys photic information to the SCN and the glutamate receptors play a critical role in mediating the response of the circadian system to photic stimulation. One of the primary goals of this proposal is to explore the possibility that glutamatergic retinal input to the SCN is rhythmic on a circadian time scale and to define the mechanisms underlying this daily regulation. Certainly understanding the mechanisms that mediate the long-term modulation of glutamatergic synaptic transmission are of general interest and importance in neuroscience research. In addition, a number of other related questions will be addressed. Is this rhythm restricted to cells in specific regions of the SCN or a general feature of synaptic communication in the SCN? Do anatomically defined cell populations within the SCN differ in their membrane properties and response to glutamatergic stimulation? Is there a daily rhythm in basal and glutamatergic-stimulated calcium levels in SCN cells? The presence of such rhythms would have important implications for information processing within the SCN but also for the cell biology of SCN neurons. Finally, the proposed work will determine whether a model developed to explain synchronization of molluscan circadian oscillators can be applied to the mammalian SCN.
