Neural coding of leg proprioception

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， 果蝇我们已经开发出新的方法来记录和操纵基因的活动- 在果蝇的本体感受回路中发现了神经元。我们将首先确定 不同的本体感受器亚型在控制肢体姿势和运动中的功能作用 行走时（目标1）。然后，我们将比较本体感受信号是如何编码， 被动和主动肢体运动（目标2），并追查电路机制， 状态依赖性本体感受编码（Aim 3）。总之，这些研究将阐明基本的 本体感受神经处理的机制，还没有可能在其他研究中进行研究。 系统.虽然苍蝇和人类在形态上存在差异， 无脊椎动物和脊椎动物躯体感觉系统的组成部分有一个惊人的共同点， 进化保守这些相似之处表明， 果蝇的神经回路将与其他动物的躯体感觉处理高度相关。一 对本体感受的深入理解有可能改变我们治疗 躯体感觉障碍

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 and manipulate the activity of genetically- identified neurons in proprioceptive circuits of behaving flies. We will first determine the functional role of distinct proprioceptor subtypes in controlling limb posture and movement during walking (Aim 1). We will then compare how proprioceptive signals are encoded during passive and active limb movements (Aim 2), and trace down the circuit mechanisms that underlie state-dependent proprioceptive coding (Aim 3). 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.