Developmental and functional analysis of neural circuits controlling navigation in Drosophila

果蝇控制导航的神经回路的发育和功能分析

• 批准号: 10444807
• 负责人: VOLKER HARTENSTEIN
• 金额: $ 53.37万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10444807
• 关键词: Address; Adult; Animal Behavior; Animals; Anterior; Back; Behavior; Behavior Control; Behavioral; Biological Metamorphosis; Brain; Complex; Cues; Data; Development; Devices; Drosophila genus; Elements; Environment; Fiber; Food; Funding; Genes; Genetic; Genetic Screening; Goals; Grant; Head; Human; Image; Inferior; Infrastructure; Interneurons; Joints; Larva; Lateral; Leg; Light; Lobe; Maps; Mediating; Medical; Microscopic; Modeling; Motor; Muscle; Mushroom Bodies; Nerve; Neurites; Neurobiology; Neurons; Neuropil; Odors; Organ; Output; Partner in relationship; Pattern; Peristalsis; Plug-in; Posture; Problem behavior; Process; Property; Recurrence; Research; Resolution; Role; Running; Sampling; Sensory; Smell Perception; Source; Synapses; System; Testing; Therapeutic; Transgenic Organisms; Trees; Update; Vision; Visual; Wing; Work; base; brain circuitry; connectome; digital; flexibility; fly; interest; larval control; member; motor control; multimodality; neural circuit; optogenetics; receptor; reconstruction; relating to nervous system; response; sensory input; sensory stimulus; source guides; spatial memory; tool; tool development; two-photon; virtual; visual map; way finding

Summary One of the most pressing research goals in neurobiology is to understand how brain circuits develop, and how these circuits control the behavior of an animal. This problem is of general importance if one wants to understand, and (therapeutically) manipulate, brain circuitry in a medical setting. A prerequisite to attain this goal is (1) the detailed mapping of complete neuron assemblies that embody specific circuits, and (2) the availability of precision tools for functional studies. Both of these conditions are now met for Drosophila. Complete connectomes (digital maps that contain all brain neurons and their synaptic connections) exist for both the larval stage (funded in part by this grant in previous years) and the adult. And in addition, genetic tools have been developed that allow one to manipulate (that is, silence, or activate) virtually every neuron, or at least neuron class, and test for the effect on specific behaviors that one is interested in. The strategy then is to extract from the connectome a wiring diagram of a specific circuit, develop hypotheses of how the different elements in the circuit interact, and use genetic tools to test these hypotheses. Studies of this proposal focus on a Drosophila brain circuit involved in navigation. Animals navigate in response to sensory stimuli in order to find food and mating partners, or avoid danger. Brain centers controlling navigation require processed, multimodal sensory input (smells, visual cues) which are integrated with proprioceptive input (feed back from muscles, joints etc) to calculate the commands required to steer the animal in the right direction. Our analysis of the larval connectome highlights a brain center called the lateral accessory lobe (LAL) as a focus of interest. We have identified the relevant LAL neuron classes and their connections, and are in the process to systematically screen for genetic constructs with which we can target these neuron classes to do functional studies. Larvae have a simple, highly quantifiable navigation behavior that allows them to find a food source (by odor) or avoid light. We will analyze how the LAL controls motor circuits that carry out this behavior. The second and third objective of the proposal is to study how the larval LAL neurons become modified and incorporated in the LAL of the adult. Adult flies have a new set of organs (e.g., wings, legs) with which to move, and receptors with which to sense; but according to our initial data, the larval neurons remain and have to adapt to cope with their new input and output. Using the connectome of the adult brain and our genetic tools we intend to identify the descendants of larval neurons in the LAL, and to address their function in adult navigation.

摘要 神经生物学中最紧迫的研究目标之一是了解大脑回路是如何发展的，以及如何 这些回路控制动物的行为。如果有人愿意的话，这个问题具有普遍的重要性 理解并(在治疗上)操纵医疗环境中的大脑回路。实现这一目标的先决条件 目标是(1)包含特定电路的完整神经元组件的详细映射，以及(2) 用于功能研究的精密工具的可用性。现在果蝇的这两个条件都得到了满足。 存在完整的连接(包含所有脑神经元及其突触连接的数字地图) 幼虫阶段(前几年的部分资金来自这笔资金)和成虫阶段。此外，基因工具 已经开发出允许人们操纵(即，沉默或激活)几乎每个神经元，或在 最少的神经元类别，并测试对一个人感兴趣的特定行为的影响。那么战略就是 从连接件中提取特定电路的接线图，开发假设如何不同 电路中的元件相互作用，并使用遗传工具来检验这些假说。 对这一提议的研究主要集中在果蝇大脑中参与导航的回路。动物导航进入 对感官刺激的反应，以寻找食物和交配对象，或避免危险。大脑中枢控制 导航需要经过处理的多模式感觉输入(气味、视觉提示)，这些输入与 本体感觉输入(从肌肉、关节等反馈)，以计算驾驶机器人所需的指令 动物的方向是正确的。我们对幼虫连接体的分析突出了一个名为侧脑室的大脑中心 副叶(LAL)作为关注焦点。我们已经确定了相关的LAL神经元类别及其 连接，并正在系统地筛选我们可以作为靶点的基因结构 这些神经元班级来做功能研究。幼虫具有简单的、高度可量化的导航行为 这使它们能够(通过气味)找到食物来源或躲避光线。我们将分析LAL是如何控制电机的 执行这一行为的回路。 该提案的第二个和第三个目标是研究幼虫LAL神经元是如何成为 修改并合并到成人的LAL中。成年果蝇有一套新的器官(如翅膀、腿) 但根据我们的初步数据，幼虫神经元仍然 并必须适应新的输入和输出。利用成人大脑的连接体和我们的 基因工具我们打算鉴定LAL中幼虫神经元的后代，并研究它们在 成人导航。