Synaptic mechanisms of touch processing in Drosophila

描述(由申请者提供)：触觉对于与现实世界的互动至关重要。为了对复杂的触觉刺激做出反应，神经系统必须整合初级机械感受器神经元群体中的尖峰模式。然而，神经系统用来检测复杂机械刺激的机制尚不清楚。为了了解中枢神经系统如何处理外周机械感觉信息，我提议研究遗传模式生物果蝇中触摸的中央编码。和哺乳动物一样，苍蝇的身体表面覆盖着主要的机械感官。在这些机械感受器中，触觉刷毛特别容易被研究，因为它们可以相互独立地受到刺激，并足以驱动姿势反射和梳理行为。然而，关于触觉刺激在刷毛或下游电路中的神经编码，人们知之甚少。我将进行实验来解决两个具体的问题：1)哪类中枢神经元整合来自机械感觉刷毛的信号；2)这些中枢神经元如何处理它们的输入来检测刷毛刺激的特定模式？为了回答第一个问题，我将筛选从机械感觉刷毛接收直接输入的中枢神经元的遗传驱动系。然后，我将使用全细胞膜片钳电生理学来研究空间和时间整合的具体机制。通过追踪感觉信号从初级感受器神经元到中枢神经系统中突触整合的流动，我希望确定神经编码的基本机制，这些机制与人类机械感觉处理的中枢障碍高度相关，如慢性疼痛和瘙痒。

DESCRIPTION (provided by applicant): The sense of touch is critical for interacting with the physical world. In order to respond to complex tactile stimuli, the nervous system must integrate patterns of spikes across populations of primary mechanoreceptor neurons. However, the mechanisms used by the nervous system to detect complex mechanical stimuli are not known. In order to understand how the central nervous system processes peripheral mechanosensory information, I propose to study the central coding of touch in the genetic model organism, Drosophila. As in mammals, the fly's body surface is covered with primary mechanosensory organs. Among these mechanoreceptors, the tactile bristles are particularly amenable to investigation because they can be stimulated independently of each other and are sufficient to drive postural reflexes and grooming behavior. Little is known, however, about the neural coding of touch stimuli within bristles or in downstream circuits. I will perform experiments to address two specific questions: 1) what classes of central neurons integrate signals from mechanosensory bristles and 2) how do these central neurons process their inputs to detect specific patterns of bristle stimulation? To answer the first question, I will screen genetic drive lines for central neurons that receive direct input from mechanosensory bristles. I will then use whole-cell patch-clamp electrophysiology to investigate specific mechanisms of spatial and temporal integration. By tracing the flow of sensory signals from primary receptor neurons to synaptic integration in the central nervous system, I hope to identify fundamental mechanisms of neural coding that are highly relevant for central disorders of mechanosensory processing in humans, such as chronic pain and itch.