Synaptic mechanisms of touch processing in Drosophila

描述（由申请人提供）：触觉是与物理世界互动的关键。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中的尖峰模式。然而，神经系统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，我建议研究遗传模式生物——果蝇的触觉中枢编码。和哺乳动物一样，苍蝇的身体表面覆盖着初级机械感觉器官。在这些机械感受器中，触觉刚毛特别适合研究，因为它们可以相互独立地受到刺激，并且足以驱动姿势反射和梳理行为。然而，对于刷毛内部或下游回路中触觉刺激的神经编码，我们所知甚少。我将通过实验来解决两个具体问题：1)哪类中枢神经元整合来自机械感觉猪鬃的信号？ 2)这些中枢神经元如何处理它们的输入以检测猪鬃刺激的特定模式？为了回答第一个问题，我将筛选从机械感觉刷毛直接接收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受体神经元到中枢神经系统突触整合的流动，我希望确定与人类机械感觉加工中枢疾病（如慢性疼痛和瘙痒）高度相关的神经编码的基本机制。

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.