A multisensory-motor integration circuit; from synapse to behavior

自然行为是运动行为的协调交响乐，这些运动行为导致自我诱导的感觉激活。感觉神经元只对感觉线索的存在和大小发出信号；它们不能区分自我诱导的输入和外部诱导的输入(例如，听到你的声音和别人的声音)。然而，动物很容易区分这些感官信号的来源；这是做出适当决策和适应行为结果的基础。神经系统通过推论放电回路区分感觉信号的来源，这是一大类神经回路，向感觉神经系统传递运动命令的“推论”，修改感觉处理。然而，人们对使相应放电回路工作的细胞和分子机制知之甚少。本项目的目的是描述一对相关的相关放电回路的结构和功能，该回路由两对已识别的组胺能神经元组成。建立一个机制框架，通过其必然的放电改变感觉功能，以优化感觉-运动性能，将解决神经系统如何整合感觉-运动信息的长期知识空白。这项研究将有助于更广泛地研究动物、机器人、无人驾驶车辆和其他运动可以与传感器功能相互作用的工程应用中的目标导向和感官导向决策。此外，这项提案还包括更广泛的社会影响，对西弗吉尼亚州本科生和研究生的STEM培训，以及为下一代神经解剖学研究制定课程。本项目旨在解决驱动必然放电电路活动的细胞和突触机制以及这种活动对感觉-运动表现的影响。为实现这一目标，将进行以下实验：1)利用连续切片电子显微镜对苍蝇脑和腹神经索进行体积重建并结合分子遗传学技术，确定2对组胺能神经元的上下游伙伴；2)利用光遗传学和钙成像技术确定上下游伙伴在高度受限驾驶线的持续行为中如何与组胺神经元相互作用；以及3)确定组胺神经元在行为分析中在塑造感觉运动表现中的作用。工作假设是，组胺神经元主要由下行的运动命令神经元激活，导致大脑中不同但相关的感觉网络的下游抑制。这个项目的基本原理是，通过精确剖析组胺神经元及其突触伙伴在特定行为背景下的相互作用，更好地理解必然放电电路如何整合和分发信息，以微调复杂自然行为中的多感觉-运动相互作用。通过建立一个机制框架，通过其必然的放电改变感觉功能，以优化感觉-运动性能，该项目提供了神经系统如何整合感觉-运动信息的知识，并有助于研究目标导向和感觉导向的决策，可应用于生物和工程应用。该项目将为学生提供STEM培训，并为新兴的连接领域提供新的课程。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Natural behaviors are a coordinated symphony of motor acts which cause self-induced sensory activation. Sensory neurons only signal presence and magnitude of a sensory cue; they cannot disambiguate self-induced from externally-induced inputs (e.g. hearing your voice versus someone else’s voice). Nevertheless, animals readily differentiate between these sources of sensory signals; this is fundamental to appropriate decision making and adaptive behavioral outcomes. Nervous systems differentiate sources of sensory signals via corollary discharge circuits, which are a broad class of neural circuits that convey a “corollary” of motor commands to sensory neural systems, modifying sensory processing. However, little is known about the cellular and molecular mechanisms that make corollary discharge circuits work. The objective of this project is to characterize the structure and function of a pair of related corollary discharge circuits, comprised of two pairs of identified histaminergic neurons. Establishing a mechanistic framework by which corollary discharges modify sensory function to optimize sensory-motor performance will address long standing gaps in knowledge of how the nervous system integrates sensory-motor information. The research will contribute to the broader study of goal-directed and sensory-guided decision making in animals, robotics, unmanned vehicles, and other engineering applications where movement can interact with sensor function. Additionally, this proposal contains broader societal impacts, STEM training for undergraduate and graduate students in West Virginia, and the development of curriculum for next generation neuroanatomical studies.This project seeks to resolve the cellular and synaptic mechanisms that drive the activity of corollary discharge circuits and the consequences of this activity for sensory-motor performance. To achieve this, experiments will be conducted to: 1) identify upstream and downstream partners of 2 pairs of histaminergic neurons using serial section electron microscopy-based volumetric reconstructions of fly brain and ventral nerve cord coupled with molecular genetic techniques; 2) determine how up- and downstream partners interact with the histamine neurons using optogenetics and Ca2+ imaging during ongoing behavior in highly restricted driver lines, and 3) determine the role of the histamine neurons in shaping sensory-motor performance in behavioral assays. The working hypothesis is that the histamine neurons are primarily activated by descending motor command neurons resulting in downstream suppression of distinct but related sensory networks in the brain. The rationale for this project is that by precisely dissecting interactions between the histamine neurons and their synaptic partners in specific behavioral contexts, a better understand of how corollary discharge circuits integrate and distribute information to fine-tune multisensory-motor interactions during complex natural behaviors. By establishing a mechanistic framework by which corollary discharges modify sensory function to optimize sensory-motor performance, this project provides knowledge of how nervous systems integrate sensory-motor information and contributes to the study of goal-directed and sensory-guided decision making, that can be applied in both biological and engineered applications. This this project will expose students to STEM training and provide new courseware for the emerging field of connectomics.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.