Gender-dimorphic Regulation of Sleep

睡眠的性别二态性调节

• 批准号: 9127364
• 负责人: Kyunghee Koh
• 金额: $ 19.5万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9127364
• 关键词: Accounting; Acetylcholine; Address; Affect; Antibodies; Arousal; Behavior; Behavioral; Biological Assay; Biological Process; Brain; Caregivers; Circadian Rhythms; Cognition; Conflict (Psychology); Courtship; Cues; Data; Dopamine; Drosophila genus; Equilibrium; Esophageal; Exhibits; Female; Gender; Genetic; Glutamates; Health; Human; Lead; Libido; Light; Modeling; Neurologic; Neurons; Neurotransmitters; Octopamine; Organism; Output; Partner in relationship; Patients; Phenotype; Population; Population Control; Quality of life; Recording of previous events; Regulation; Reproductive Behavior; Research; Sex Characteristics; Signal Transduction; Site; Sleep; Sleep Deprivation; Sleep Disorders; Staining method; Stains; Synapses; System; Techniques; Testing; Time; Wakefulness; Work; base; fly; gamma-Aminobutyric Acid; gender difference; insight; male; mating behavior; neural circuit; neuromechanism; neurotransmission; novel; novel strategies; reconstitution; relating to nervous system; sleep regulation; tool; transcription factor; transgene expression

 DESCRIPTION (provided by applicant): Sleep is an essential biological process that is conserved from flies to humans. Studies of sleep regulation have focused on two main mechanisms: the circadian mechanism that controls when to sleep and the homeostatic mechanism that regulates how much to sleep. Nevertheless, other factors, such as gender, also affect sleep, but the mechanism underlying gender-dimorphic sleep regulation is poorly understood. This proposal aims to investigate a novel Drosophila neural circuit involved in male-specific regulation of sleep. We recently identified a small number of neurons in the brain whose activation leads to markedly reduced sleep in male flies, but not in female flies. This is exciting because although several sleep-regulatory neuronal centers have been identified in Drosophila, this is the first example of a gender-dimorphic arousal center. Our preliminary data suggest that the newly identified arousal center promotes wakefulness in the presence of females and makes synaptic contacts with neurons that express the male-specific transcription factor FruitlessM, which is required for male courtship behavior. To understand how this novel arousal center regulates sleep in a gender-dimorphic manner, several key questions need to be addressed. What are the input signals and behavioral outputs of this neural center? What other neuronal populations does the neural center connect to and which neurotransmission system does it employ? We will address these questions using an array of genetic tools that are available for circuit analysis in Drosophila. This work will investigate a novel neural circuit involved in male-specific regulation of sleep and will produce new research avenues for understanding sex differences in sleep. Further, this work may provide valuable insights into the fundamental problem of how the brain balances competing needs to decide on appropriate behaviors.

 描述（由申请人提供）：睡眠是从果蝇到人类都保留的一个重要的生物过程。睡眠调节的研究主要集中在两个主要机制上：控制何时睡觉的昼夜节律机制和调节睡眠时间的稳态机制。然而，其他因素，如性别，也会影响睡眠，但性别二态性睡眠调节的机制尚不清楚。该提案旨在研究一种涉及男性特异性睡眠调节的新型果蝇神经回路。我们最近在大脑中发现了少量神经元，它们的激活会导致雄性果蝇的睡眠显着减少，但雌性果蝇则不会。这很令人兴奋 因为尽管在果蝇中发现了几个睡眠调节神经元中心，但这是性别二态性唤醒中心的第一个例子。我们的初步数据表明，新发现的唤醒中心在雌性存在的情况下促进觉醒，并与表达雄性特异性转录因子 FruitlessM 的神经元进行突触接触，这是雄性求爱行为所必需的。为了了解这种新颖的唤醒中心如何以性别二态的方式调节睡眠，需要解决几个关键问题。这个神经中枢的输入信号和行为输出是什么？神经中枢还连接哪些其他神经元群体以及它采用哪种神经传递系统？我们将使用一系列可用于果蝇回路分析的遗传工具来解决这些问题。这项工作将研究一种涉及男性特异性睡眠调节的新型神经回路，并将为理解睡眠中的性别差异提供新的研究途径。此外，这项工作可能为大脑如何平衡竞争需求以决定适当行为的基本问题提供有价值的见解。