Circadian rhythms are endogenous physiological and behavioral rhythms with a period of approximately 24 hours. Difficulty shifting circadian rhythms has been hypothesized to underlie the impaired performance and discomfort induced in humans by either crossing several time zones or working shift schedules. The mammalian circadian system may be thought of as consisting of three parts; a pacemaker, input pathways which can phase shift and entrain the pacemaker, and output pathways by which the pacemaker can influence the rest of the brain. Many type of evidence indicate that the cells of the hypothalamic suprachiasmatic nucleus (SCN) constitute the major pacemaker. The experiments that I am proposing are designed to answer several specific questions. The research will focus on a single input pathway to the suprachiasmatic nuclei from cells in the lateral geniculate nucleus (the geniculo-hypothalamic tract or GHT), and a single output pathway from the suprachiasmatic nucleus to the hypothalamic subparaventricular area. My research will answer three questions about the GHT of the hamster. 1) What are the responses of SCN cells to a peptide contained in GHT terminals? 2) How do visual responses of GHT neurons compare with those of SCN neurons? 3) How does GHT input affect visual responses of SCN neurons? Other experiments will address two questions about the projection of SCN neurons to the subparaventricular area. 1) What are the neuropharmacological characteristics of this projection? 2) How does this output pathway function in the control of circadian rhythms? In the studies proposed here, I will use golden hamsters, either in lesion-behavior studies with wheeling-running activity measured, or in electrophysiological preparations (both in vivo and in vitro). The golden hamster is an appropriate animal model for the study of mammalian circadian rhythms, in large part because the hamster exhibits very precise behavioral rhythms in wheel-running activity. A wealth of previous literature on formal and physiological aspects of hamster circadian systems and the many parallels among the hamster circadian system and circadian systems of other mammals, including that of humans, help to make the hamster particularly useful.
