RESTORATION OF CIRCADIAN RHYTHMICITY BY SUPRACHIASMATIC TISSUE GRAFTS

每天的生物节律由位于 下丘脑的视交叉上核。因此，损伤的 SCN废除了运动活动、车轮运行、 皮质醇、褪黑素、体温等。进一步有力的证据表明 SCN包含每日生物钟，由 胎儿SCN组织移植恢复昼夜节律的观察 在有SCN损伤的宿主动物中，轮子运行。自从胎儿SCN移植物 恢复昼夜节律振荡和由 振荡，不仅是时钟，而且还有新的连接 时钟和直接控制测量行为的站点，已经被 已经成立了。本项目的目的是调查a) 节律(如体温、荷尔蒙、行为)由SCN恢复 移植和b)修复的时间进程。 以前的实验集中在单个时钟驱动的过程(例如 车轮运行或睡眠唤醒)以评估SCN移植物的成功。在……里面 我们的实验将同时测量多个(行为、 生理、神经内分泌)不同起源的节律，以便 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)。在早期 SCN移植实验中，很难区分 供体组织恢复昼夜节律振荡，并重新表达 由于SCN不完整而引起的宿主昼夜节律振荡 损伤。自杂合型tau突变体的昼夜节律以来 仓鼠“有22个小时的异常短时间，我们将 将tau突变仓鼠的SCN组织移植到SCN损伤区 野生型仓鼠。二十二小时节律的表达式将是 作为SCN移植成功的标志。从这个过程中学到的知识 本实验将有助于研究SCN传出神经在脑内的作用。 SCN移植物对昼夜节律性的恢复及其作用 通过完整的SCN控制昼夜节律性。 在过去的一年里，我们制定了必要的方法来 持续同时监测人体的昼夜节律 体温、运动、尿糖皮质激素和尿量 单个仓鼠体内的褪黑素。这一方法将应用于 下一年研究昼夜节律的功能恢复 接受SCN移植的SCN损伤仓鼠的节律。

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.