The Neural Basis of Spontaneous Action

自发行动的神经基础

基本信息

批准号：
10056793
负责人：
Michael H Dickinson
金额：
$ 45.79万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-15 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10056793
关键词：
ARNT gene Ablation Anatomy Animals Antibodies Architecture Atmosphere Behavior Behavioral Biophysics Brain Cell model Cell physiology Cells Chronic Collection Cues Denmark Development Diagnosis Drosophila genus Exhibits Flying body movement Foundations Frequencies Functional Imaging Generations Genetic Genetic Models Gilles de la Tourette syndrome Goals Grant Human Huntington Disease Image Impairment Individual Interneurons Label Lateral Lead Learning Lighting Lobe Maps Measures Modeling Molecular Nervous system structure Neurons Neuropil Noise Parkinson Disease Pattern Physiological Physiology Process Psychophysics Reagent Research Role Saccades Sensory Side Stains Structure Synaptic Transmission System Techniques Testing The Sun Time Work design experimental study fly in vivo innovation member motor learning nervous system disorder optogenetics patch clamp polarized light relating to nervous system screening sensory stimulus statistics synaptotagmin tool two-photon

项目摘要

Project Summary Although behavior is largely structured by sensory cues, animals also benefit from random actions. Stochastic actions and variability are important for many behaviors including motor learning, search, and predator evasion. Furthermore, understanding the cellular basis of stochasticity may be pertinent to many neurological disorders involving the inability to either suppress or generate involuntary actions, including Tourette's syndrome, Huntington's chorea, and Parkinson's disease. Despite its importance, the mechanisms underlying the generation of random actions at the molecular, cellular, or network levels are poorly understood. Understanding spontaneous processes in the nervous system will benefit from research in a tractable genetic model in which both its functional role and mechanistic basis could be studied vertically across phenomenological levels. Recently, a genetically identified neuron has been identified cell (called DNa04) in the fruit fly, Drosophila that serves as a command neuron for rapid spontaneous turns, called saccades. This is a rare case of a single genetically identified neuron whose activity is necessary and sufficient for stochastic actions. Although it is already possible to record from this command neuron using 2-photon imaging and in vivo patch clamp, the primary goal of this proposal is to identify members of the upstream network that is responsible for generating its stochastic activity. Toward these goals, Specific Aim 1 of this proposal will focus on screening a collection of ~20 selective split-GAL4 lines labeling interneurons in the Lateral Accessory Lobe (LAL), the upstream neuropil region that is thought responsible for generating the spontaneous activity in the DNa04 cell. We will perform 2- photon functional imaging in intact flying flies to record from LAL interneurons and use genetic tracing techniques including trans-Tango to map the connectivity within the network. In Specific Aim 2 we will explore the function of individual cells in generating the pattern of spontaneous activity by manipulating cell physiology using a variety approaches including optogenetic activation and silencing. Specific Aim 3 will focus on psychophysical experiments aimed at quantifying and modeling the influence of sensory stimuli that modulate the frequency of spontaneous saccades. By mapping the network and experimentally manipulating the physiology of its member cells, we will lay the foundation for developing a quantitative model of the cellular basis of spontaneous actions in the brain.

项目概要尽管行为很大程度上是由感官线索决定的，但动物也能从随机行为中受益。随机动作和变化对于许多行为都很重要，包括运动学习、搜索和躲避捕食者。此外，了解随机性的细胞基础可能与许多神经系统疾病有关涉及无法抑制或产生非自愿行为，包括抽动秽语综合症，亨廷顿舞蹈病和帕金森病。尽管它很重要，但其背后的机制人们对分子、细胞或网络水平上随机行为的产生知之甚少。理解神经系统中的自发过程将受益于易处理的遗传模型的研究，其中它的功能作用和机制基础都可以在现象学层面进行垂直研究。最近，在果蝇（果蝇）中发现了一种经过基因鉴定的神经元细胞（称为 DNA04），该细胞充当快速自发转动的命令神经元，称为扫视。这是罕见的单一案例基因识别的神经元，其活动对于随机行为是必要且充分的。虽然它是已经可以使用 2 光子成像和体内膜片钳从该命令神经元进行记录，该提案的主要目标是确定负责生成的上游网络的成员它的随机活动。为了实现这些目标，本提案的具体目标 1 将重点筛选一系列约 20 个选择性分裂 GAL4 线标记侧副叶 (LAL)（上游神经毡）中的中间神经元该区域被认为负责在 DNA04 细胞中产生自发活动。我们将执行2- 完整飞行果蝇的光子功能成像，记录 LAL 中间神经元并使用遗传追踪技术包括 trans-Tango 来映射网络内的连接。在具体目标 2 中，我们将探索该函数通过使用各种方法操纵细胞生理学，单个细胞产生自发活动的模式方法包括光遗传学激活和沉默。具体目标 3 将侧重于心理物理学旨在量化和模拟调节频率的感觉刺激的影响的实验自发性眼跳。通过绘制网络图并通过实验操纵其成员的生理机能细胞，我们将为开发自发行为的细胞基础的定量模型奠定基础在大脑中。