CAREER: Mechanistic dissection of sleep and behavioral arousal: A model system approach to interdisciplinarity in neuroscience research and education

睡眠和觉醒是高度保守和基本的行为状态。调节这些状态以响应环境条件和稳态需求的能力对于生存至关重要。目标导向的动机行为，如交配、进食和攻击，本质上依赖于强烈的行为唤醒。尽管如此，我们对区分和协调动机过程与睡眠-觉醒调节的神经机制知之甚少。在这里，研究人员通过研究睡眠的行为协调和社会行为（如求爱），使用果蝇的实验易处理性来确定唤醒状态是如何编码和整合大脑中的行为的。专注于生物体中具有可测量行为输出的小电路，这些电路适合遗传操作和神经生理学记录，从而产生资源和专业知识，使初中，高中，本科和研究生能够进行跨学科研究。该项目的研究和教育计划协同作用，以支持女性，少数民族和第一代大学生通过研究参与，职业指导，技能培训，跨学科思维和包容性教学实践来整合跨学科的技能和概念。睡眠和行为唤醒协调的电路机制在任何生物中都不为人所知。该项目的重点是定义睡眠和觉醒在苍蝇大脑中编码的电路机制，以及它们如何因果地影响与求爱和攻击等动机性社会行为相关的唤醒状态。该研究小组已经确定了整合神经元，这些神经元编码了求爱的动机，也调节了觉醒和唤醒。本项目研究这些整合神经元启动和维持唤醒的机制，以共同调节睡眠表达与动机行为。研究人员已经建立了果蝇作为睡眠和行为觉醒的共同调节的电路分析的有利模型，通过开发新的行为测定，工具来靶向单个细胞类型和记录这种共同调节不稳定的网络活动。在目标1和2中，研究绘制了整合器P1网络与时钟网络、蘑菇体和中枢复合体的睡眠调节神经元之间的兴奋性和抑制性突触相互作用，这些神经元是睡眠和社会行为双向控制的基础。在目标3中，对具有不稳定的睡眠或社会唤醒状态的识别的微电路动物的自发神经活动进行测量。该项目将建立基因，电路和行为之间的联系，以了解内部状态依赖的决策和行动选择。 该项目还使初中、高中、本科和研究生接触跨学科研究。一个关键的重点是支持女性，少数民族和第一代大学生通过研究参与，职业指导，技能培训，跨学科思维和包容性教学实践来整合跨学科的技能和概念。这个奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持的。

Sleep and wakefulness are highly conserved and fundamental behavioral states. The ability to regulate these states in response to environmental conditions and homeostatic needs is critical for survival. Goal-directed motivated behaviors like mating, feeding and aggression are essentially dependent on strong behavioral arousal. Nonetheless, little is known about the neuronal mechanisms that compartmentalize and coordinate motivational processes with sleep-wake regulation. Here, the investigators determine how arousal states are encoded and integrated across behaviors in the brain by studying the behavioral coordination of sleep and social behaviors like courtship using the experimental tractability of the fruit fly Drosophila. The focus on small circuits with measurable behavioral outputs in organisms amenable to genetic manipulations and neurophysiological recordings generates resources and expertise that exposes middle-school, high-school, undergraduate and graduate students to interdisciplinary research. The research and educational programs in this project act synergistically to support female, minority, and first-generation college students to integrate skills and concepts across disciplines through research engagement, career mentoring, skills-training, interdisciplinary thinking, and inclusive teaching practices.Circuit mechanisms underlying the coordination of sleep and behavioral arousal are not understood in any organism. The focus of this project is to define the circuit mechanisms by which sleep and wake are encoded in the fly brain and how they causally influence arousal states associated with motivated social behaviors like courtship and aggression. The research team has identified integrator neurons that encode motivation to court and also mediate wakefulness and arousal. This project investigates the mechanisms by which these integrator neurons initiate and maintain arousal to co-regulate sleep expression with motivated behaviors. The investigators have established Drosophila as an advantageous model for circuit analysis of co-regulation of sleep and behavioral arousal by developing novel behavioral assays, tools to target individual cell-types and record network activity where this co-regulation has been destabilized. In Aims 1 and 2, studies map excitatory and inhibitory synaptic interactions between integrator P1 network and sleep-regulating neurons of clock network, Mushroom Body and Central Complex that underlies the bidirectional control of sleep and social behaviors. In Aim 3, measurements are made of the spontaneous neural activity of identified microcircuits animals with destabilized sleep- or social-arousal states. This project will establish connections between genes, circuits, and behavior in understanding internal state dependent decision making and action-selection. The project also exposes middle-school, high-school, undergraduate and graduate students to interdisciplinary research. A key focus is supporting female, minority, and first-generation college students to integrate skills and concepts across disciplines through research engagement, career mentoring, skills-training, interdisciplinary thinking, and inclusive teaching practices.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.