Integration of sleep-regulating signals by the Drosophila Pars Intercerebralis

果蝇脑间部整合睡眠调节信号

• 批准号: 9303232
• 负责人: Annika Fitzpatrick Barber
• 金额: $ 2.34万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2016-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9303232
• 关键词: Ablation; Address; Affect; Amides; Area; Arousal; Behavior; Behavioral Genetics; Biological Assay; Brain; Brain region; Calcium; Cells; Chronic; Circadian Rhythms; Computer Simulation; Data; Dorsal; Drosophila genus; Electrophysiology (science); Genetic; Goals; Health; Homeostasis; Homologous Gene; Hypothalamic structure; Image; Insulin; Light; Maps; Measures; Memory; Metabolism; Molecular; Nervous system structure; Neurons; Organism; Output; Pathway interactions; Peptide Receptor; Peptide Signal Sequences; Peptides; Performance; Physiologic pulse; Physiological Processes; Physiology; Population; Process; Response to stimulus physiology; Rest; Role; Shapes; Signal Transduction; Sleep; Sleep Deprivation; Sum; Synapses; System; Testing; Time; Visual; Wakefulness; Work; analog; arm; base; circadian pacemaker; cognitive function; disorder prevention; falls; fly; immune function; knock-down; member; memory consolidation; neural circuit; neuroregulation; novel; patch clamp; receptor; research study; response; simulation; sleep regulation

 DESCRIPTION (provided by applicant): Although sleep is a fundamental process involved in survival and proper brain performance, how the brain determines when to fall asleep and wake up is still not understood. The importance of sleep is further underscored by accumulating evidence that sleep deprivation and circadian rhythm disruption contributes to chronic health issues, due to the role of sleep in many physiological processes including metabolism, immune function, memory consolidation and more. Sleep results from the sum of information from two systems: the circadian clock and the sleep homeostatic system. The circadian system contains a core molecular clock that is synchronized to the time of day by visual inputs and drives a 24h rhythm in many physiological processes and behaviors, including sleep. The sleep homeostasis system signals the need to sleep after prolonged wakefulness. How and where homeostatic and circadian information are integrated to drive sleep is not known. The central hypothesis of this proposal is that the Pars Intercerebralis (PI), an analog of the mammalian hypothalamus, receives and integrates both circadian and homeostatic information. The PI is involved in controlling both amount of sleep, which is a measure of the homeostatic system, as well as circadian timing of sleep. The PI is part of a circadian output pathway controlling rest-activity rhythms and likely receives input from multiple areas, including the core circadian clock and regions involved in sleep homeostasis. PI output is largely in the form of peptides released from distinct PI cell populations. These peptide signals may have diverse targets inside and outside the nervous system. The aims of this project are 1) To determine whether the firing of PI cells reflects circadian control; 2) To determine whether the firing behavior of PI cells is also affecte by the sleep homeostat and 3) To map the putative interactions of circadian and homeostatically controlled PI cells. To pursue these aims, a combination of Drosophila genetics and behavior, electrophysiology and calcium imaging will be used. Understanding the neural circuits involved in making sleep-wake decisions will open the door to novel hypotheses of how to influence these decisions to aid in healthy sleep and disease prevention.

 描述（由适用提供）：尽管睡眠是涉及生存和适当大脑表现的基本过程，但大脑如何确定何时入睡和唤醒仍未了解。由于睡眠剥夺和昼夜节律干扰的累积证据进一步强调了睡眠的重要性，这是由于睡眠在许多身体过程中的作用，包括代谢，免疫功能，记忆巩固等，这会导致慢性健康问题。睡眠来自两个系统的信息总和：昼夜节律时钟和睡眠稳态系统。昼夜节律系统包含一个核心分子时钟，该时钟通过视觉输入与一天中的时间同步，并在包括睡眠在内的许多物理过程和行为（包括睡眠）中驱动24小时的节奏。睡眠体内稳态系统表明长时间的清醒需要睡觉。尚不清楚安装式和昼夜节律信息如何以及在哪里集成到睡眠。该提议的中心假设是，哺乳动物下丘脑的类似物卷脑（PI）接收和整合了昼夜节律和稳态信息。 PI参与控制睡眠量，这是衡量体内稳态系统的量度以及昼夜节律的睡眠时间。 PI是昼夜节律途径的一部分，该途径控制着静止的节奏，并可能从多个区域（包括核心昼夜节律时钟和涉及睡眠体内平衡的区域）接收输入。 PI输出很大程度上以从不同PI细胞种群释放的宠物形式。这些肽信号可能在神经系统内外具有潜水员的靶标。该项目的目的是1）确定PI细胞的发射是否反映了昼夜节律的控制； 2）确定PI细胞的发射行为是否也会受到睡眠体内平衡的影响和3）绘制昼夜节律和稳态控制的PI细胞的假定相互作用。为了追求这些目标，将使用果蝇遗传学和行为，电生理学和钙成像的结合。了解做出睡眠效果决策所涉及的神经元电路将为如何影响这些决策以帮助健康睡眠和预防疾病的新假设打开大门。