RESTORATION OF CIRCADIAN RHYTHMICITY BY SUPRACHIASMATIC TISSUE GRAFTS

每天的生物节律是由一个生物钟控制的， 下丘脑的视交叉上核。 因此， SCN消除了运动活动、轮跑 皮质醇，褪黑激素，体温等。进一步有力的证据表明， SCN包含的每日生物钟是由 观察到胎儿SCN组织移植物恢复了 在SCN损伤的宿主动物中的轮跑。 因为胎儿SCN移植 恢复了昼夜节律振荡和行为驱动的 振荡，不仅是时钟，而且是新的连接之间的 时钟和网站直接控制测量的行为，已被 确立了习 本项目的目的是调查a）哪些 SCN可恢复节律（如体温、激素、行为） 移植物和B）恢复的时间过程。 先前的实验集中于单个时钟驱动的过程（例如， 轮跑或睡眠-觉醒）以评估SCN移植物的成功。 在 我们的实验将同时测量多个（行为， 生理，神经内分泌）不同起源的节奏，以 确定SCN移植物恢复昼夜节律输出的程度 系统（例如，车轮运行，大脑温度和褪黑激素）。 月初 SCN移植实验中，很难区分 通过供体组织恢复昼夜节律振荡， 由于SCN不完整， 损伤。 由于杂合的“tau突变体”的昼夜节律周期 仓鼠“有一个不正常的22小时短，我们将 将来自tau突变仓鼠的SCN组织移植到SCN损伤的仓鼠中， 野生型仓鼠 22小时节奏的表达将是 用作SCN移植成功的标志物。 从这件事中获得的知识 实验将是有价值的，在检查SCN传出的作用， SCN移植物恢复昼夜节律性及其作用 通过完整的SCN控制昼夜节律。 去年，我们制定了必要的方法， 连续并同时监测体内的昼夜节律 体温、运动活动、尿皮质类固醇和尿 一只仓鼠体内的褪黑素 这一方法将用于 第二年调查昼夜节律的功能恢复 已接受SCN移植物的SCN损伤的仓鼠中的节律。

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.