NEURAL BASIS OF BIOLOGICAL RHYTHMS

昼夜节律是行为中内部产生的节律， 生理周期约为24小时。 对潜在风险的认识 昼夜节律对于所有药物治疗都是必不可少的。 昼夜节律可用于医学治疗， 例如，通过定时给药以最小化毒副作用。 内部节奏必须重新设定以保持与外部同步 24小时循环。 更好地理解重置机制将 允许在与时差有关的不适的治疗方面取得进展 和轮班工作，以及各种抑郁症。 几种类型的刺激能够相移生物钟。 光主要在主观夜间产生相移， 特征相位响应曲线（PRC），“LPRC.“其他刺激， 包括暗脉冲，在一个新的运行轮内的活动， 苯二氮卓类药物注射，主要在 主观的一天，在“DPRC”模式。 哺乳动物的昼夜节律起搏器位于下丘脑 视交叉上核（SCN）。 我建议测量昼夜节律 振荡从SCN维持在体外，并研究相位 由各种神经递质引起的变化。 我将用这个模型来 研究伴随着昼夜节律的相移的细胞事件 在LPRC或DPRC模式中的时钟。 以下表征 与这些PRC中的任何一个相关的刺激，然后我将确定 这些刺激对（a）立即早期基因的诱导，（B） 细胞外放电率，和（c）SCN神经元的膜电位。 这项工作将导致更好地了解重置和节奏- 哺乳动物昼夜节律的产生机制。

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.