Neural coding of leg proprioception

腿部本体感觉的神经编码

• 批准号: 9361774
• 负责人: John Tuthill
• 金额: $ 33.91万
• 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/9361774
• 关键词: Alpha Cell; Anatomy; Animal Model; Animals; Axon; Behavior Control; Calcium; Cells; Code; Computer Analysis; Confocal Microscopy; Development; Disease; Drosophila genus; Drosophila melanogaster; Electrophysiology (science); Employee Strikes; Feedback; Future; Gene Expression Profile; Genetic; Genetic Models; Goals; Health; Human; Image; Image Analysis; Invertebrates; Investigation; Knowledge; Label; Leg; Limb structure; Logic; Magnetism; Maps; Mechanical Stimulation; Methods; Morphology; Movement; Nervous system structure; Neuraxis; Neurons; Patients; Peripheral; Peripheral Nerves; Population; Positioning Attribute; Posture; Process; Proprioception; Proprioceptor; Research; Role; Sensory; Signal Transduction; Somatosensory Disorders; Spatial Distribution; Stimulus; Synapses; System; Techniques; Testing; Therapeutic; Vertebrates; Work; arm movement; body position; cell type; chronic pain; design; experimental study; fly; improved; in vivo; innovation; insight; intersectionality; limb movement; motor control; neural circuit; neuromechanism; optogenetics; patch clamp; 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 本体感觉，即对自我运动和身体位置的感觉，对于有效控制至关重要 运动行为。缺乏本体感受反馈的人，例如外周神经系统疾病患者， 神经损伤，无法保持肢体姿势或协调的精细规模的运动， 胳膊和腿但是，尽管本体感觉对所有人的运动控制都很重要， 动物，很少有人知道神经计算的基础肢体本体感觉在任何 动物这一差距是由于两个基本的挑战：（1）确定特定的神经细胞类型， 检测和处理本体感受信号，以及（2）记录来自本体感受信号的神经活动。 自然肢体运动时的回路在此，我们建议通过以下方式克服这些挑战： 在遗传模式生物果蝇中研究腿部本体感觉的神经编码， 果蝇我们已经开发了新的方法来记录从基因识别的神经元， 本体感受电路与体内电生理学和2光子成像，而 用磁力控制系统操纵腿的位置和运动。在目标1中，我们将使用 2-光子钙成像确定本体感受神经编码的空间组织 在一群机械感觉神经元中。在目标2中，我们将使用钙成像来测试 假设腿部本体感觉的特定参数，如位置和运动， 是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 来自不同的机械感觉神经元亚型的信号被整合的假设， 下游神经元，使用光遗传学和全细胞膜片钳电生理学。 总之，这些研究将阐明本体感受神经加工的基本机制 这是在其他系统中无法研究的。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， 躯体感觉系统有着惊人的进化保守性。这些相似之处表明 在果蝇的电路中发现的一般原则将与 其他动物的躯体感觉处理。对本体感觉的更深入理解 有可能改变我们治疗躯体感觉障碍的方式。