Mechanisms of Active Sensing in Drosophila

果蝇主动感知机制

• 批准号: 10589901
• 负责人: MARIE SUVER
• 金额: $ 24.37万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589901
• 关键词: Afferent Neurons; Animals; BRAIN initiative; Behavior; Behavioral; Biological Models; Brain; Cell model; Cells; Characteristics; Closure by clamp; Data; Disease; Drosophila genus; Drosophila melanogaster; Electrophysiology (science); Environmental Wind; Esthesia; Failure; Fingers; Flying body movement; Genetic; Genetic Models; Goals; Grant; Hand; Human; Immunohistochemistry; Insecta; Label; Learning; Location; Machine Learning; Measures; Mechanoreceptors; Mediating; Mentors; Mission; Modeling; Molecular; Motor; Motor Neurons; Movement; Muscle; Nervous System; Nervous System Physiology; Neurons; Neurotransmitters; Odors; Phase; Population; Postdoctoral Fellow; Process; Regulation; Research; Resolution; Role; Schizophrenia; Sensory; Shapes; Signal Transduction; Speed; Stains; Stimulus; Study models; System; Testing; Touch sensation; Translating; Video Recording; Walking; Work; active control; autism spectrum disorder; expectation; experimental study; fly; goal oriented behavior; insight; machine learning algorithm; model organism; neural circuit; novel; optogenetics; response; sensor; sensory integration; sensory stimulus; tool

Project Summary The goal of this project is to study the cellular basis of active sensation. A crucial function of all nervous systems is to distinguish between sensory stimuli originating from the external world and that generated by our own movements. This task relies on brain circuits that integrate sensory information with an internal model, or expectation, of self-generated movements. The complexity and intractability of many models used to study active sensing means that translating insights from these studies to failures of normal nervous system function remains challenging. Fruit flies (Drosophila melanogaster) actively move their antennae, and my recent work has elucidated a neural circuit that processes mechanosensory information from the antenna. Given the power of Drosophila as a genetic model organism, this project aims to develop the neural circuits controlling and sensing antennal movement as a cellular model for studying principles of active sensing. In the K99 (mentored) portion of this grant, I will identify the cellular location at which self- versus externally-generated mechanosensory signals become differentially represented in the brain. I will make electrophysiological recordings of intracellular activity from 2nd and 3rd order mechanosensory neurons and compare how these two populations encode passive and active movements of the antennae. I will distinguish between these two types of movements using machine learning analysis of simultaneously recorded video data. For the R00 (independent) phase, I will use optogenetics and immunohistochemistry to identify motor neurons that control antennal movement. I will then ask where input from motor neurons impinge on the sensory circuit. Finally, I will test the role of active antennal movements in behavior. By perturbing active antennal movements in freely walking and flying flies, I will directly test how these movements enable different behavioral tasks such as wind orientation and obstacle avoidance. Together, these experiments will identify the cellular basis for active sensing in Drosophila, and their role in goal- oriented behaviors.

项目摘要 该项目的目的是研究主动感觉的细胞基础。所有神经系统的关键功能 是区分源自外部世界的感觉刺激和我们自己产生的刺激 动作。此任务依赖于将感官信息与内部模型集成到的大脑电路，或 期望，自我生成的运动。许多用于研究主动的模型的复杂性和顽固性 感应意味着将这些研究的见解转化为正常神经系统功能的失败 具有挑战性的。水果蝇（果蝇Melanogaster）积极移动触角，我最近的工作有 阐明了一个神经回路，该神经回路从天线处理机械感应信息。鉴于 果蝇作为遗传模型有机体，该项目旨在开发控制和传感的神经回路 触角运动是研究主动传感原理的细胞模型。在K99（指导）部分 在这笔赠款中，我将确定自我与外部生成的机械感应信号的蜂窝位置 在大脑中差异代表。我将进行细胞内活性的电生理记录 从第二和第三阶机械感觉神经元开始，并比较这两个种群如何编码被动和 触角的主动运动。我将使用机器区分这两种类型的运动 同时记录的视频数据的学习分析。对于R00（独立）阶段，我将使用 光遗传学和免疫组织化学识别控制触角运动的运动神经元。然后我会 询问运动神经元的输入在感觉电路上。最后，我将测试主动触角的作用 行为运动。通过在自由步行和飞翔的苍蝇中扰动主动触角运动，我将直接 测试这些运动如何实现不同的行为任务，例如风向和避免障碍物。 这些实验将共同确定果蝇中主动传感的细胞基础，以及它们在目标中的作用 定向行为。