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.

概括 神经生物学中最紧迫的研究目标之一是了解脑电路的发展方式，以及如何 这些电路控制动物的行为。如果一个人想 在医疗环境中理解和（治疗）操纵脑电路。实现这一目标的先决条件 目标是（1）体现特定电路的完整神经元组件的详细映射，以及（2） 用于功能研究的精确工具的可用性。现在，果蝇都满足了这两种情况。 存在完整的连接组（包含所有脑神经元及其突触连接的数字图） 幼虫阶段（部分由往年的赠款资助）和成人。此外，遗传工具 已经开发了一种允许一个人（即，沉默或激活）几乎每个神经元或在 至少神经元类，并测试对一个人感兴趣的特定行为的影响。然后 从连接组提取特定电路的接线图，提出假设的假设 电路中的元素相互作用，并使用遗传工具来检验这些假设。 该提案的研究集中在涉及导航的果蝇脑电路上。动物驶入 对感官刺激的反应，以找到食物和交配伴侣，或避免危险。大脑中心控制 导航需要与之整合的经过处理的多峰感觉输入（气味，视觉提示） 本体感受的输入（从肌肉，关节等回馈）以计算转向所需的命令 动物朝正确的方向。我们对幼虫连接组的分析突出了一个称为侧向的大脑中心 附件叶（LAL）作为感兴趣的重点。我们已经确定了相关的LAL神经元及其 连接，并且正在系统地筛选我们可以针对的遗传结构 这些神经元类进行功能研究。幼虫具有简单，高度可量化的导航行为 这使他们可以找到食物来源（气味）或避免光。我们将分析LAL如何控制电动机 执行此行为的电路。 该提案的第二和第三目标是研究幼虫LAL神经元如何变成 修改并纳入成人的lal。成人苍蝇有一套新的器官（例如，翅膀，腿） 要移动的东西，以及可以感知的受体；但是根据我们的最初数据，幼虫神经元仍然存在 并且必须适应应对其新输入和输出。使用成人大脑和我们的连接组 我们打算确定LAL中幼虫神经元的后代，并解决其功能 成人导航。