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Sexually-Dimorphic Regulation of Sleep

睡眠的性别二态性调节

基本信息

批准号：
10475646
负责人：
Kyunghee Koh
金额：
$ 34.13万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-17 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10475646
关键词：
ARNT gene Abdomen Affect Anatomy Arousal Attenuated Behavior Behavioral Biological Assay Biological Models Books Brain Brain region Calcium Caregivers Caring Complex Conflict (Psychology)Courtship Data Dopamine Drosophila genus Elderly Equilibrium Female Ganglia Generations Goals Homeostasis Human Image Immunohistochemistry Individual Knowledge Lead Libido Mediating Mind Modeling Motivation Neurologic Neuromodulator Neurons Norepinephrine Octopamine Organism Outcome Study Partner in relationship Pathway interactions Patients Peptides Physiological Population Process Quality of life Reproduction Reproductive Behavior Role Sex Differences Sexual Partners Signal Pathway Signal Transduction Site Sleep Sleep Deprivation Sleep Disorders Synapses Techniques Testing Text Wakefulness Work dopaminergic neuron egg experimental study fascinate fitness fly insight male neuromechanism novel novel strategies reproductive sex sexual dimorphism sleep behavior sleep pattern sleep regulation transcription factor

项目摘要

Sleep is essential for healthy mind and body. It is regulated by homeostasis, by which accumulated sleep drive during wakefulness leads to increased propensity toward sleep. However, we can stay up late if we have something important or interesting to do, for example, take care of a baby or read a fascinating book. In other words, sleep is also regulated by motivational states. Thus sleep drive competes with other motivational drives to decide whether we sleep or engage in other important or interesting activities. We have recently shown that sex drive profoundly affects male sleep in Drosophila and that a subset of octopaminergic neurons (octopamine is analogous to human norepinephrine) mediates sleep suppression by male sex drive. Previous studies have shown that female flies sleep less and lay more eggs after mating. Thus both males and females adjust their sleep patterns to meet reproductive needs. However, the neural mechanisms of how sleep and reproductive behaviors are balanced are not well understood. In preliminary studies for this proposal, we identified several previously uncharacterized neuronal populations for balancing sleep and reproductive behaviors in males and females. Two of the newly identified populations are dopaminergic, suggesting that octopamine and dopamine signaling pathways cooperate to integrate sleep and reproductive behaviors. We will determine the anatomical and physiological connectivity among the various neuronal populations, and investigate their role in sleep and reproductive behaviors using a combination of behavioral analysis, calcium imaging, circuit tracing, immunohistochemistry, and generation of new drivers for precise manipulation of specific neurons. Our proposed studies offer an excellent opportunity to discover basic neural mechanisms and general organizing principles that underlie the balance between competing drives. Investigating how sleep regulatory mechanisms communicate with neural mechanisms for sexually-dimorphic behaviors using neuromodulators such as octopamine and dopamine may lead to a better understanding of how the human brain integrates sleep drive and other motivational states.

睡眠对身心健康是必不可少的。它是由动态平衡调节的，通过它积累清醒时的睡眠驱动力会导致睡眠倾向的增加。然而，我们可以熬夜迟到如果我们有重要的或有趣的事情要做，例如，照顾孩子或阅读一本令人着迷的书。换句话说，睡眠也受激励状态的调节。因此睡眠驱动力与其他激励动力竞争，以决定我们是睡觉还是从事其他重要的或有趣的活动。我们最近发现，性欲对男性睡眠有深远的影响。果蝇和章鱼能神经元的一个子集(章鱼类似于人类去甲肾上腺素)通过男性性欲调节睡眠抑制。此前的研究表明，雌性苍蝇交配后睡眠较少，产卵较多。因此，男性和女性都调整了他们的睡眠模式，以满足生殖需求。然而，睡眠和睡眠的神经机制生殖行为是平衡的还没有被很好地理解。在对这项提案的初步研究中，我们确定了几个以前没有描述过的神经元群体，它们可以平衡睡眠和雄性和雌性的生殖行为。其中两个新发现的种群是多巴胺能，提示章鱼胺和多巴胺信号通路协同整合睡眠和生殖行为。我们将确定解剖和生理上的连通性在不同的神经元群体中，并研究它们在睡眠和生殖中的作用使用行为分析、钙成像、电路跟踪、免疫组织化学，以及精确操纵特定神经元的新驱动因素的产生。我们提出的研究提供了一个很好的机会来发现基本的神经机制和一般组织原则，这些原则构成了相互竞争的动力之间的平衡。研究睡眠是如何调节机制与神经机制沟通的性二态行为使用神经调节剂，如章鱼胺和多巴胺，可能会更好地理解人脑将睡眠驱动和其他激励状态结合在一起。