NEURAL BASIS OF BIOLOGICAL RHYTHMS

昼夜节律是内部产生的行为节律和 周期大约24小时的生理学。对潜在问题的认识 昼夜节律性对于所有药物治疗都是必不可少的。 昼夜节律可以在医疗中发挥优势，例如 例如，通过定时给药，将毒副作用降至最低。 必须重置内部节奏以保持与外部节奏的同步 周期为24小时。更好地理解重置机制将 允许在治疗与时差相关的不适方面取得进展 以及倒班工作，以及各种抑郁障碍。 有几种类型的刺激能够使生物钟相移。 光主要在主观的夜晚产生相移， 特征相响应曲线(PRC)，即“LPRC”。其他刺激， 包括暗脉冲，在新的转轮内的活动，以及 注射苯二氮卓类药物，主要在 主观日，在“DPRC”句型中。 哺乳动物的昼夜节律起搏器位于下丘脑。 视交叉上核(SCN)我提议测量昼夜节律 SCN在体外维持的振荡和研究时相 由各种神经递质引起的移位。我将使用这个模型来 研究伴随着昼夜节律相移的细胞事件 时钟模式为LPRC或DPRC。以下是对 与这两个PRC相关的刺激，然后我将确定 这些刺激对(A)即刻早期基因的诱导，(B) 细胞外放电频率；(C)SCN神经元的膜电位。 这项工作将导致对重置和节奏的更好理解-- 哺乳动物昼夜节律性的发生机制。

Circadian rhythms are internally generated rhythms in behavior and physiology with periods of about 24 hours. Awareness of underlying circadian rhythmicity is essential for all pharmacological treatments. Circadian rhythms can be used to advantage in medical treatments, for example, by timing drug delivery to minimize toxic side effects. Internal rhythms must be reset to maintain synchrony with the external cycle of 24 h. Better understanding of the resetting mechanisms will allow advances in the treatment of discomforts associated with jet lag and shift work, as well as a variety of depressive disorders. Several types of stimuli are able to phase shift the circadian clock. Light produces phase shifts mainly during the subjective night, with a characteristic phase response curve (PRC), the "LPRC." Other stimuli, including dark pulses, activity within a novel running wheel, and benzodiazepine injections, produce phase shifts mainly during the subjective day, in the "DPRC" pattern. The mammalian circadian pacemaker is localized to the hypothalamic suprachiasmatic nuclei (SCN). I am proposing to measure circadian oscillations from the SCN maintained in vitro and to study the phase shifts induced by various neurotransmitters. I will use this model to study the cellular events which accompany phase shifts of the circadian clock in either the LPRC or DPRC pattern. Following characterization of the stimuli associated with either of these PRCs, I will then determine effects of these stimuli on (a) induction of immediate early genes, (b) extracellular firing rate, and (c) membrane potential of SCN neurons. This work will lead to a better understanding of resetting and rhythm- generating mechanisms underlying mammalian circadian rhythmicity.