RESTORATION OF CIRCADIAN RHYTHMICITY BY SUPRACHIASMATIC TISSUE GRAFTS

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Daily biological rhythms are controlled by a biological clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The results of several types of experiments indicate the daily biological clock resides within the SCN. Lesions of the SCN abolish circadian rhythms of motor activity, wheel-running, cortisol, melatonin, body temperature, etc. Further 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. SCN grafts restore both the circadian clock (measured indirectly as a self-sustained circadian oscillation in wheel-running) as well as efferent fiber or endocrine linkage between the clock, and the brain nuclei which more directly control output behaviors. 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 are simultaneously measuring behavioral, physiological, and neuroendocrine rhythms in order to determine a) whether SCN grafts restore multiple outputs of the circadian system (e.g. wheel-running, brain temperature, and melatonin), and b) the time courses required for circadian rhythm restoration. Fetal SCN tissue of the heterozygous "tau mutant hamster" is used as donor tissue since the clock of this hamster strain has a shortened circadian period that is easily distinguished from the circadian rhythm of incomplete SCN-lesioned, wild-type hamsters. The expression of a twenty-two hour rhythm can then 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. We have previously demonstrated the feasibility of collecting, and assaying simultaneous circadian profiles of urinary 6-sulphatoxymelatonin and urinary cortisol in single hamsters. Using recently developed experimental apparatus, during the coming year circadian rhythms in body temperature, motor activity, urinary corticosteroids, and urinary melatonin will be simultaneously collected in intact and in SCN-lesioned hamsters. We anticipate that in the future, this apparatus can be used to measure the restoration of circadian endocrine profiles in graft recipient hamsters.