Synaptic mechanisms of touch processing in Drosophila

果蝇触觉处理的突触机制

• 批准号: 8782828
• 负责人: John Tuthill
• 金额: $ 5.33万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8782828
• 关键词: Action Potentials; Address; American; Animal Model; Axon; Behavior; Body Surface; CNS processing; Cells; Characteristics; Code; Complex; Deep Brain Stimulation; Disease; Drosophila genus; Drosophila melanogaster; Electrophysiology (science); Exhibits; Frequencies; GABA Receptor; Genetic; Genetic Models; Genetic Screening; Grooming; Human; Individual; Investigation; Ion Channel; Label; Lead; Leg; Mammals; Maps; Measures; Mechanics; Mechanoreceptors; Medical; Motion; Movement; Nervous system structure; Neuraxis; Neurons; Organ; Pattern; Peripheral; Peripheral Nervous System; Phase; Population; Process; Property; Reflex action; Sensory; Signal Transduction; Skin; Stimulus; Surface; Synapses; System; Tactile; Testing; Thalamic structure; Therapeutic Intervention; Time; Touch sensation; Unconscious State; chronic pain; experience; fly; in vivo; neuromechanism; painful neuropathy; patch clamp; public health relevance; receptive field; receptor; relating to nervous system; research study; response; sensory stimulus

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.

描述（由申请人提供）：触觉对于与物理世界互动至关重要。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神经元群体的尖峰模式。然而，神经系统用于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，我建议研究遗传模型生物果蝇中触觉的中枢编码。与哺乳动物一样，苍蝇的体表覆盖着主要的机械感觉器官。在这些机械感受器中，触觉刷毛特别适合研究，因为它们可以彼此独立地受到刺激，并且足以驱动姿势反射和梳理行为。然而，人们对刷毛内或下游电路中触摸刺激的神经编码知之甚少。我将进行实验来解决两个具体问题：1）哪些类别的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其输入以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鬃毛直接输入的中枢神经元的遗传驱动线。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处理中枢疾病（例如慢性疼痛和瘙痒）高度相关的神经编码基本机制。