The Neural Basis of Spontaneous Action

项目摘要 虽然行为在很大程度上是由感官线索构成的，但动物也从随机的行为中受益。随机性 动作和可变性对许多行为都很重要，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疾病有关。 包括无法抑制或产生非自愿行为，包括多发性抽动症， 亨廷顿舞蹈症和帕金森氏症。尽管它很重要，但背后的机制 分子、细胞或网络水平上的随机行为的产生还知之甚少。理解 神经系统的自发过程将受益于对易处理的遗传模型的研究，在该模型中 它的功能作用和机制基础都可以跨现象学层面进行纵向研究。 最近，在果蝇中发现了一种经遗传鉴定的神经元(称为DNa04)，这种细胞 作为快速自发转弯的指挥神经元，称为扫视。这是一例罕见的单发 基因识别的神经元，其活动对于随机行为是必要的和充分的。尽管它是 已经可以使用双光子成像和活体膜片钳从这个命令神经元记录， 该提案的主要目标是确定负责发电的上游网络成员 它的随机活动。为了实现这些目标，本提案的具体目标1将侧重于筛选一系列 ~20个选择性Split-GAL4标记上游神经纤维束--副叶外侧核的中间神经元 被认为负责在DNa04细胞中产生自发活动的区域。我们将表演2- 完整飞行苍蝇的光子功能成像记录LAL中间神经元并使用遗传示踪技术 包括Trans-Tango以映射网络内的连接性。在具体目标2中，我们将探索其功能 通过使用各种不同的方式操纵细胞生理学来产生自发活动模式的单个细胞 方法包括光遗传激活和沉默。具体目标3将侧重于心理物理 旨在量化和模拟感官刺激的影响的实验，这些刺激调制了 自发的扫视。通过绘制网络图并通过实验操作其成员的生理 细胞，我们将为建立自发行为的细胞基础的量化模型奠定基础 在大脑里。

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.