NEURAL BASIS OF BIOLOGICAL RHYTHMS

描述（改编自申请人摘要）：内部生成 昼夜节律每天通过外部线索重新设定，以维持24小时 周期 相移响应通常取决于昼夜节律相位，其可以是 相位响应曲线（PRC）。 当光与 一个PRC（光或LPRC），其他刺激产生不同的，非光 PRC（非光或DPRC）。 与之相关的生理事件 这些行为表达的相移模式并不好 明白 哺乳动物的昼夜节律起搏器位于下丘脑 视交叉上核 视交叉上核细胞维持一个 体外自持振荡，允许相移测量 一个孤立的时钟。 测量昼夜节律时钟相移 在体外，通过从视交叉上神经元采集自发活动， 在施加相移刺激之后的脑切片制备。 这种生物钟的体外模型可用于研究 光和非光相移剂。 谷氨酸和神经肽Y 将分别用作光剂和非光剂。 拟议 研究将揭示介导光和非光相的机制， 转移 具体问题包括：1. 有什么影响 神经肽Y对视交叉上核神经元的影响 2. 有哪些 光和非光相移之间的异同？ 3. 在什么时候光和非光相移路径相互作用？ 昼夜节律的紊乱可能是不适的基础 与时差和轮班工作有关，以及各种抑郁症 紊乱 昼夜节律是许多重要医学事件的基础， 治疗的昼夜节律时间已被有益地应用于化疗 癌症治疗 更深入地了解内在组织和 哺乳动物昼夜节律系统的相位重置特性将有助于 时间生物学的进一步临床应用

DESCRIPTION (adapted from applicant's abstract): Internally generated circadian rhythms are reset each day by external cues to maintain a 24 h cycle. Phase shift responses often depend on circadian phase, which can be described in a phase-response curve (PRC). While light is associated with one PRC (the photic or LPRC), other stimuli produce a different, non-photic PRC (the non-photic or DPRC). The physiological events associated with these behaviorally expressed phase-shifting patterns are not well understood. The mammalian circadian pacemaker is located in the hypothalamic suprachiasmatic nuclei. Suprachiasmatic nuclei cells maintain a self-sustained oscillation in vitro, allowing measures of phase-shifting behavior from an isolated clock. Circadian clock phase shifting is measured in vitro by sampling spontaneous activity from suprachiasmatic neurons in the brain slice preparation following application of phase-shifting stimuli. This in vitro model of the circadian clock can be used to study effects of photic and non-photic phase-shifting agents. Glutamate and neuropeptide Y will be used as photic and non-photic agents, respectively. The proposed studies will uncover mechanisms mediating photic and non-photic phase shifting. Specific questions include: 1. What are the effects of neuropeptide Y on suprachiasmatic nuclei neurons? 2. What are the similarities and differences between photic and non-photic phase shifts? 3. At what point do photic and non-photic phase-shifting pathways interact? Disturbances in the phasing of circadian rhythms may underlie discomforts associated with jet lag and shift work, as well as various depressive disorders. Circadian rhythms underlie many important medical events and circadian timing of treatments has been profitably applied in chemotherapy cancer treatment. Greater knowledge of the intrinsic organization and the phase resetting properties of the mammalian circadian system will aid in further clinical applications of chronobiology.