Neural coding of leg proprioception

腿部本体感觉的神经编码

• 批准号: 10200156
• 负责人: John Tuthill
• 金额: $ 34.02万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200156
• 关键词: Anatomy; Animal Model; Animals; Axon; Calcium; Cells; Code; Computer Analysis; Confocal Microscopy; Development; Disease; Drosophila genus; Drosophila melanogaster; Electrophysiology (science); Feedback; Future; Gene Expression Profile; Genetic; Genetic Models; Goals; Health; Human; Image; Invertebrates; Investigation; Knowledge; Label; Leg; Limb structure; Logic; Magnetism; Maps; Mechanical Stimulation; Methods; Morphology; Movement; Nervous system structure; Neuraxis; Neurons; Patients; Peripheral; Population; Positioning Attribute; Posture; Process; Proprioception; Proprioceptor; Research; Role; Sensory; Signal Transduction; Somatosensory Disorders; Spatial Distribution; Stimulus; Structure; Synapses; System; Techniques; Testing; Therapeutic; Vertebrates; Work; arm movement; body position; cell type; chronic pain; design; experimental study; fly; improved; in vivo; innovation; insight; limb movement; motor behavior; motor control; neural circuit; neuromechanism; optogenetics; patch clamp; peripheral nerve damage; relating to nervous system; response; somatosensory; tool; two-photon

Project Summary Proprioception, the sense of self-movement and body position, is critical for the effective control of motor behavior. Humans lacking proprioceptive feedback, such as patients with peripheral nerve damage, are unable to maintain limb posture or coordinate fine-scale movements of the arms and legs. But despite the importance of proprioception to the control of movement in all animals, little is known about the neural computations that underlie limb proprioception in any animal. This gap is due to two basic challenges: (1) identifying specific neuronal-cell types that detect and process proprioceptive signals, and (2) recording neural activity from proprioceptive circuits during natural limb movements. Here, we propose to overcome these challenges by investigating the neural coding of leg proprioception in a genetic model organism: the fruit fly, Drosophila. We have developed new methods to record from genetically-identified neurons in proprioceptive circuits with in vivo electrophysiology and 2-photon imaging, while manipulating leg position and movement with a magnetic control system. In Aim 1, we will use 2-photon calcium imaging to define the spatial organization of proprioceptive neural coding within a population of mechanosensory neurons. In Aim 2, we will use calcium imaging to test the hypothesis that specific parameters of leg proprioception—such as position and movement— are encoded by genetically distinct subtypes of mechanosensory neurons. In Aim 3, we will test the hypothesis that signals from distinct mechanosensory neuron subtypes are integrated by downstream neurons, using optogenetics and whole-cell patch-clamp electrophysiology. Altogether, these studies will elucidate basic mechanisms of proprioceptive neural processing that have not possible to investigate in other systems. Although there are morphological differences between flies and humans, the basic building blocks of invertebrate and vertebrate somatosensory systems share a striking evolutionary conservation. These similarities suggest that the general principles discovered in circuits of the fruit fly will be highly relevant to somatosensory processing in other animals. A deeper understanding of proprioception has the potential to transform the way in which we treat somatosensory disorders.

项目概要 本体感觉，即自我运动和身体位置的感觉，对于有效控制至关重要 的运动行为。缺乏本体感觉反馈的人类，例如周围神经障碍患者 神经损伤，无法维持肢体姿势或协调肢体的精细运动 手臂和腿。但是，尽管本体感觉对于所有运动的控制都很重要 对于动物来说，我们对任何动物肢体本体感觉背后的神经计算知之甚少。 动物。这一差距是由于两个基本挑战造成的：（1）识别特定的神经元细胞类型 检测和处理本体感受信号，以及（2）记录本体感受的神经活动 自然肢体运动期间的电路。在此，我们建议通过以下方式克服这些挑战： 研究遗传模型生物体中腿部本体感觉的神经编码：果蝇， 果蝇。我们开发了新方法来记录基因识别的神经元 具有体内电生理学和 2 光子成像的本体感觉电路，同时 通过磁性控制系统操纵腿部位置和运动。在目标 1 中，我们将使用 2 光子钙成像定义本体感觉神经编码的空间组织 在机械感觉神经元群体内。在目标 2 中，我们将使用钙成像来测试 腿部本体感觉的特定参数（例如位置和运动）的假设 由遗传上不同的机械感觉神经元亚型编码。在目标 3 中，我们将测试 来自不同机械感觉神经元亚型的信号通过以下方式整合的假设 下游神经元，利用光遗传学和全细胞膜片钳电生理学。 总而言之，这些研究将阐明本体感觉神经处理的基本机制 不可能在其他系统中进行调查。虽然有形态上的 苍蝇和人类之间的差异，无脊椎动物和脊椎动物的基本组成部分 体感系统具有惊人的进化保守性。这些相似之处表明 在果蝇电路中发现的一般原理将与 其他动物的体感处理。对本体感觉有更深入的了解 有可能改变我们治疗体感疾病的方式。