NEURAL BASIS OF BIOLOGICAL RHYTHMS

描述(改编自申请者摘要)：内部生成 昼夜节律每天由外部信号重置，以维持24小时 周而复始。相移响应通常取决于昼夜节律相位，这可能是 在相响应曲线(PRC)中描述。虽然光与 一个PRC(光的或LPRC)，其他刺激产生不同的、非光的 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不是很好 明白了。 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 体外自维持振荡，允许相移测量 来自孤立时钟的行为。测量昼夜节律时钟相移 取大鼠视交叉上核神经元的自发活动进行体外实验 相移刺激后脑片的制备。 这种生物钟的体外模型可以用来研究 光性和非光性相移剂。谷氨酸与神经肽Y 将分别用作透光剂和非透光剂。建议数 研究将揭示光和非光相的调节机制 换档。具体问题包括：1.这些措施有哪些影响 视交叉上核神经元上的神经肽Y？2.什么是 光相移和非光相移的异同？ 光和非光相移路径在什么点上相互作用？ 昼夜节律的节律紊乱可能是导致不适的原因 与时差和倒班工作以及各种抑郁有关 精神错乱。昼夜节律是许多重要医学事件的基础 昼夜节律治疗已经在化疗中得到了有益的应用 癌症治疗。更多地了解内部组织和 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.