Neural coding of leg proprioception

腿部本体感觉的神经编码

基本信息

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
项目类别：
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

项目摘要

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缺乏本体感觉反馈的人类，例如外周病患者。神经损伤，无法维持肢体姿势或协调肢体的精细运动但尽管本体感觉对于控制所有运动都很重要。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。这种差距是由于两个基本挑战造成的：（1）识别特定的神经细胞类型。检测和处理本体感受信号，以及（2）记录本体感受的神经活动在这里，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，我们开发了新方法来记录果蝇中基因鉴定的神经元。具有体内电生理学和 2 光子成像的本体感觉电路，同时在目标 1 中，我们将使用磁力控制系统来操纵腿部位置和运动。 2 光子钙成像定义本体感觉神经编码的空间组织在目标 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，我们将进行测试。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尽管存在形态学，但无法在其他系统中进行研究。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这些相似之处表明体感系统具有惊人的进化保守性。在果蝇电路中发现的一般原理将与对其他动物的体感处理有更深入的了解。有可能改变我们治疗体感疾病的方式。