RESTORATION OF CIRCADIAN RHYTHMICITY BY SUPRACHIASMATIC TISSUE GRAFTS

点击翻译按钮获取中文摘要

Daily biological rhythms are controlled by a biological clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Thus, lesions of the SCN abolish circadian rhythms in motor activity, wheel-running, cortisol, melatonin, body temperature, etc. Further strong evidence that the SCN contains the daily biological clock is provided by the observation that fetal SCN tissue grafts restore circadian rhythms of wheel-running in SCN-lesioned host animals. Since the fetal SCN graft restores both the circadian oscillation and the behavior driven by the oscillation, not only the clock but also new connections between the clock and sites directly controlling the measured behavior, have been established. The purpose of this project is to investigate a) which rhythms (e.g. body temperature, hormonal, behavioral) are restored by SCN grafts and b) the time course of the restoration. Previous experiments focused on a single clock driven process (e.g. wheel-running or sleep-wake) to assess the success of the SCN graft. In our experiments we will simultaneously measure multiple (behavioral, physiological, neuroendocrine) rhythms of distinct origin in order to determine the extent to which SCN grafts restore outputs of the circadian system (e.g. wheel-running, brain temperature, and melatonin). In early SCN graft experiments, there was difficulty distinguishing between the restoration of a circadian oscillation by donor tissue, and re-expression of the host circadian oscillation as a result of an incomplete SCN lesion. Since the circadian period of the heterozygous "tau mutant hamster" has an abnormally short period of twenty-two hours, we will transplant SCN tissue from the tau mutant hamster into SCN-lesioned wild-type hamsters. The expression of a twenty-two hour rhythm will be used as a marker of a successful SCN graft. Knowledge gained from this experiment will be valuable in examining the role of SCN efferents in the restoration of circadian rhythmicity by SCN grafts, as well as their role in the control of circadian rhythmicity by intact SCN. In the past year we have developed the methodology necessary to continuously and simultaneously monitor circadian rhythms in body temperature, motor activity, urinary corticosteroids, and urinary melatonin in an individual hamster. This methodology will be applied in the next year to investigate the functional restoration of circadian rhythms in SCN-lesioned hamsters that have received SCN grafts.