NEURAL BASIS OF MAMMALIAN CIRCADIAN ORGANIZATION

哺乳动物昼夜节律组织的神经基础

• 批准号: 6230954
• 负责人: GENE D BLOCK
• 金额: $ 28.9万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-22 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6230954
• 关键词: Mammalia; age difference; bioperiodicity; biophysics; brain electrical activity; brain mapping; circadian rhythms; developmental neurobiology; gene expression; hypothalamus; laboratory mouse; laboratory rat; microelectrodes; nervous system; neural plasticity; neuroanatomy; neurogenetics; neurons; neurophysiology; photobiology; photostimulus; reporter genes; stimulus interval; suprachiasmatic nucleus; tissue /cell culture

The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus is part of a system that controls the near 24-hour (circadian) rhythms in many physiological processes and behaviors. This timing system generates circadian behaviors, synchronizes them to local time, sets an appropriate phase relationship between each behavior and daily environmental cycles, and sculpts the duration and amplitude of each behavior in response to particular environmental conditions (e.g., seasonal photoperiod). Although it is highly likely that individual SCN neurons generate circadian periodicities, it is uncertain whether these complex circadian behaviors arise at the level of single cells, through cellular interactions within the SCN tissue, or through interactions with other neural and/or non-neural systems. Furthermore, the pathways and mechanisms by which the SCN conveys timing information to other brain regions remain largely unexplored. The proposed experiments will examine the circadian properties and mechanisms of intercellular communication of neurons in vivo, and in cultured tissues and dispersals. Changes in the duration of the photoperiod or period of the light:dark cycle result in classically described changes in the time of activity onset, the duration of activity, or the expressed period of activity rhythms. Specific aim 1 will determine the level of cellular organization and mechanisms responsible for maintaining an appropriate phase relationship between the behavior and local time, the kinetics of resynchronization (e.g., phase shifting transients), and the control of circadian waveform by entraining stimulus parameters. Specific aim 2 will address the neural origins of plasticity in circadian behavior. We will determine whether changes in period and waveform are generated at the level of single SCN neurons, within the SCN or at other levels of neural organization. Finally, specific aim 3 will determine the locus of age-related deterioration of some of the behaviors examined in specific aims 1 and 2. These experiments will be aided greatly by the recent development of new technologies that enable recording of cellular rhythmicity for weeks in vitro. We will measure molecular rhythmicity by monitoring per1:luciferase activity in transgenic cells and electrical activity from individual neurons using multielectrode arrays. These procedures allow us to record from neurons taken from animals at least 9 months of age. Taken together, these studies will provide insights into how different levels of neural organization contribute to the generation and control of mammalian circadian behaviors.

哺乳动物下丘脑的视交叉上核（SCN）是控制许多生理过程和行为中近24小时（昼夜）节律的系统的一部分。 该计时系统生成昼夜节律行为，将它们与当地时间相匹配，在每个行为和日常环境周期之间设置适当的相位关系，并响应于特定的环境条件（例如，季节性光周期）。虽然个体SCN神经元很可能产生昼夜节律周期性，但不确定这些复杂的昼夜节律行为是否在单细胞水平上通过SCN组织内的细胞相互作用或通过与其他神经和/或非神经系统的相互作用而产生。此外，SCN向其他大脑区域传递时间信息的途径和机制在很大程度上仍未被探索。 拟议的实验将检查在体内，并在培养的组织和分散的神经元细胞间通信的昼夜节律的属性和机制。光周期或光暗周期持续时间的变化导致活动开始时间、活动持续时间或活动节律的表达周期的经典描述的变化。 具体目标1将确定细胞组织的水平和负责维持行为和局部时间之间的适当相位关系的机制，代谢的动力学（例如，相移瞬变），以及通过引入刺激参数来控制昼夜节律波形。 具体目标2将解决昼夜节律行为可塑性的神经起源。 我们将确定周期和波形的变化是否在单个SCN神经元的水平上产生，在SCN内或在神经组织的其他水平上产生。 最后，具体目标3将决定具体目标1和2中所考察的某些行为与年龄有关的恶化的发生地点。 这些实验将大大有助于最近发展的新技术，使记录细胞的节奏数周的体外。 我们将通过监测转基因细胞中的per 1：荧光素酶活性和使用多电极阵列的单个神经元的电活性来测量分子节律性。 这些程序使我们能够记录从至少9个月大的动物身上提取的神经元。 总之，这些研究将提供深入了解不同水平的神经组织如何有助于哺乳动物昼夜节律行为的产生和控制。