NEURAL BASIS OF BIOLOGICAL RHYTHMS

生物节律的神经基础

• 批准号: 2460448
• 负责人: MARY E HARRINGTON
• 金额: $ 7.02万
• 依托单位: SMITH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2460448
• 关键词: biological clocks; circadian rhythms; hamsters; membrane potentials; neurotransmitters; photostimulus; regulatory gene; suprachiasmatic nucleus; tissue /cell culture

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.

昼夜节律是内部产生的行为节奏和 生理学大约24小时。 意识到基础 昼夜节律对于所有药理治疗都是必不可少的。 昼夜节律可用于在医疗治疗中优势 例如，通过定时输送药物来最大程度地减少毒性副作用。 内部节奏必须重置以保持与外部的同步 循环24小时。 更好地了解重置机制将 允许治疗与喷气滞后相关的不适 和转变工作以及各种抑郁症。 几种类型的刺激能够相移昼夜节律。 光主要在主观的夜晚产生相偏移， 特征相响应曲线（PRC），“ LPRC”。 其他刺激， 包括深色脉冲，新颖的跑步轮活动以及 注射苯二氮卓，主要在 主观的一天，以“ DPRC”模式。 哺乳动物昼夜节律起搏器位于下丘脑 超型核（SCN）。 我建议衡量昼夜节律 SCN的振荡维持体外并研究了阶段 各种神经递质诱导的移位。 我将使用此模型 研究伴随昼夜节律相移的细胞事件 以LPRC或DPRC模式为时钟。 以下表征 与这两种PRC相关的刺激，我将确定 这些刺激对（a）诱导直接早期基因的影响，（b） 细胞外发射速率和（c）SCN神经元的膜电位。 这项工作将使人们更好地理解重置和节奏 生成哺乳动物昼夜节律的基础机制。