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.

项目摘要 本体感受，自动移动和身体位置的感觉，对于有效的控制至关重要 运动行为。人类缺乏本体感受反馈，例如外周患者 神经损伤，无法维持肢体姿势或协调的精细运动 手臂和腿。但是，尽管本体感受对控制所有运动的控制很重要 动物，对任何肢体本体感受的神经计算知之甚少 动物。此差距是由于两个基本挑战所致：（1）确定特定的神经元细胞类型 检测和过程本体感受信号，以及（2）从本体感受中记录神经活动 自然肢体运动中的电路。在这里，我们建议通过 研究遗传模型有机体中腿本体感受的神经化：果蝇， 果蝇。我们开发了新方法来记录从遗传鉴定的神经元中的记录 体内电生理学和2光子成像的本体感受电路，而 通过磁控制系统来操纵腿部位置和运动。在AIM 1中，我们将使用 2光子钙成像以定义本体感受性神经编码的空间组织 在机理感知神经元的种群中。在AIM 2中，我们将使用钙成像进行测试 腿本体感受（例如位置和运动）的特定参数的假设 由机械感觉神经元的遗传学亚型编码。在AIM 3中，我们将测试 来自不同机制神经元亚型信号的假设是由 下游神经元，使用光遗传学和全细胞斑块钳电生理学。 总之，这些研究将阐明本体感受性神经加工的基本机制 在其他系统中不可能进行调查。虽然有形态学 苍蝇和人类之间的差异，无脊椎动物和脊椎动物的基本构件 体感系统具有惊人的进化保护。这些相似之处暗示 在果蝇圈中发现的一般原则将与 其他动物的体感处理。对本体感受的更深入了解 改变我们处理体感障碍的方式的潜力。