Identifying, manipulating, and studying a complete sensory-to-motor model behavior circuit

识别、操作和研究完整的感觉到运动模型行为回路

• 批准号: 10449063
• 负责人: LISA STOWERS
• 金额: $ 10万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10449063
• 关键词: Achievement; Administrative Supplement; Animals; Area; Autopsy; Behavior; Brain; Brain imaging; Brain region; Code; Complement; Complex; Coupled; Cues; Data; Data Analyses; Decision Making; Development; Environment; Equipment; Esthesia; Fiber; Functional disorder; Funding; Goals; Human Resources; Image; Individual; Learning; Link; Logic; Maps; Mediating; Methods; Modeling; Monitor; Motor; Motor output; Mus; Muscle; Neurons; Parents; Pattern; Photometry; Preparation; Protocols documentation; Proxy; Public Health; Reporting; Research; Resolution; Resources; Sensory; Signal Transduction; Social Behavior; Standardization; System; Time; Ultrasonography; United States National Institutes of Health; Update; Visualization; Work; awake; brain surgery; cost; experience; high resolution imaging; imaging approach; in vivo imaging; information model; motivated behavior; neural circuit; neural correlate; neuromechanism; parent grant; parent project; programs; relating to nervous system; tool

PROJECT SUMMARY We are requesting supplemental funds to obtain and apply transformative, recently validated methods to identify and study the neural correlates of behavior. How does the brain transform sensory information into complex behavior? The objective of the parent proposal is to identify the relevant neurons across the brain that are necessary to produce a relatively simple motivated behavior to study and identify fundamental principles underlying coding. Sensory-to- behavior circuits contain a variety of neural computations such as those that determine the identity and meaning of the sensed cues, gauge internal state, remember previous experience, and command muscle action. In the parent proposal we aim to identify and study an entire circuit from sensation across the brain to motor output. The original RFA called for the ability to leverage and study neural dynamics. At the time of the funding of the parent grant, we proposed to monitor brain-wide activity using cFos as a proxy, however this only provides a snapshot of an instant of brain activity in post-mortem animals. We complemented this approach with in vivo imaging of GCaMP activity by fiber photometry in awake behaving animals. This method reveals neural dynamics over seconds but is limited to image a small subset of the brain. Though these methods were state of the art at the time, they are both low through-put to implement and do not provide neural dynamics across the whole brain. Recently, functional ultrasound imaging (fUSi) has been validated to report dynamic images of the entire mouse brain (4 times/second) with a resolution of at least 100um. Dynamic, whole brain, high resolution imagine is truly transformative. fUSi is relatively easy and low-cost which will reduce resources including personnel, animals, and time. It will not just be faster and easier; we will learn more. We expect the additional information provided by fUSi to increase the confidence and scope of our conclusions. This will enable unprecedented activity profiles to inform all of our original aims including identifying key neural circuits and nodes, information flow within nodes and across the brain, and the change in activity with development and experience in and across individuals. Moreover, dynamic brain wide activity correlated with behavior will increase our ability to generate reliable models of information coding. Better models are expected to provide new, testable hypothesis that will benefit our understanding of information coding of sensory and social behavior and of brain function in general. An administrative supplement to implement this approach will result in more rapid achievement of our aims and better facilitate the goals of the initial RFA.

项目摘要 我们要求补充资金以获取和应用变革性，最近经过验证 识别和研究行为神经相关的方法。大脑如何变化 感官信息到复杂行为？父母建议的目的是确定 整个大脑中相关的神经元是产生相对简单的必需的 研究和确定编码基本原则的动机行为。感觉到 - 行为电路包含各种神经计算，例如确定的神经计算 感知线索的身份和含义，衡量内部状态，记住以前的经验， 并指挥肌肉动作。在父母的建议中，我们旨在识别和研究整个 从跨大脑到电动机输出的电路。原始RFA要求能够 杠杆和研究神经动力学。在父母赠款的资助时，我们提出了 要使用CFO作为代理监测大脑的活动，但这仅提供 验尸后动物的脑活动瞬间。我们用体内补充了这种方法 在醒着的行为动物中，通过纤维光度法对GCAMP活性进行成像。此方法揭示了 神经动力学在几秒钟内，但仅限于大脑的一小部分。虽然这些 当时的方法是艺术的状态，它们都无法实施，而不是 在整个大脑中提供神经动力学。最近，功能性超声成像（FUSI） 已经过验证以报告整个鼠标大脑的动态图像（4次/秒） 分辨率至少为100UM。动态，全脑，高分辨率想象是真的 变革性。 FUSI相对容易且低成本，这将减少资源 人员，动物和时间。它不仅会更快，更容易；我们将学习更多。我们期望 FUSI提供的其他信息以增加我们的信心和范围 结论。这将使前所未有的活动概况告知我们所有最初的目标 包括识别关键的神经回路和节点，节点内以及跨越整个 大脑，以及随着个人和跨个体的发展和经验而进行的活动变化。 此外，动态大脑活动与行为相关，将增加我们的能力 生成可靠的信息编码模型。期望更好的模型提供新的， 可检验的假设将有利于我们对感官信息编码和 社会行为和大脑功能一般。执行此项的行政补充 方法将使我们的目标更快地实现，并更好地促进目标的目标 初始RFA。