Structural and functional development of touch sensory neurons

触觉感觉神经元的结构和功能发育

• 批准号: 9904782
• 负责人: Celine Santiago
• 金额: $ 1.58万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904782
• 关键词: Adult; Affect; Affective; Afferent Neurons; Anatomy; Axon; Behavior; Brain; Brain Stem; Complement; Development; Disease; Electrophysiology (science); Genetic; Goals; Injury; Label; Life; Manuals; Mechanoreceptors; Mediating; Monitor; Morphogenesis; Morphology; Mus; Natural regeneration; Nature; Nerve; Neuraxis; Neurons; Painless; Pattern; Peripheral; Positioning Attribute; Process; Property; Quality of life; Research; Role; Sensory; Skin; Social Behavior; Spinal Cord; Stimulus; Structure; Synapses; Tactile; Testing; Time; Touch sensation; Visualization; Whole-Cell Recordings; cell type; design; dorsal horn; experimental study; in vivo; motor control; mouse genetics; nerve supply; neural prosthesis; postnatal development; receptive field; relating to nervous system; response; sensory stimulus; somatosensory; synaptogenesis; tool

Our sense of touch is essential for our ability to perform fine manual tasks and for affective behaviors, and disruptions in tactile sensitivity can profoundly affect quality of life. Low-threshold mechanoreceptor (LTMR) neurons detect non-painful tactile stimuli in the periphery and transmit this information to the central nervous system (CNS). Our lab has produced genetic tools that enable visualization and functional manipulation of the major LTMR subtypes in the mouse, revealing that primary LTMR afferents transmit highly organized information about the nature and position of the touch stimulus they detect. However, the mechanisms that establish LTMR connectivity in the CNS to produce the functional organization of mechanosensory inputs remain unknown. In particular, the role of neural activity during LTMR morphogenesis, central targeting, and synaptogenesis has not been tested. The goal of my proposed research is to characterize the structural and functional development of LTMR neurons, and to test the role of activity in establishing organized patterns of LTMR connectivity in the CNS. Aim 1 will use genetic tools to characterize the acquisition of LTMR morphologies and central targeting patterns, as well as synapse formation between LTMRs and their CNS targets. In Aim 2 I will use electrophysiological recordings to monitor the maturation of functional response properties in LTMRs, and will generate genetic tools to investigate the role of neural activity during LTMR central targeting and synaptogenesis. Together, my proposed research will define how the circuits that process tactile stimuli are established to allow for the exquisite spatial and functional organization of somatosensory representations in the CNS. Understanding how touch circuits are assembled during development will guide research efforts aimed at promoting the regeneration of sensory axons following nerve damage in conditions of injury or disease, as well as the design of effective neural prosthetics to restore sensory function.

我们的触觉对于我们完成精细的手工任务和情感行为的能力至关重要， 触觉敏感性的中断可以深刻地影响生活质量。低阈值机械感受器 神经元检测到周围的非疼痛性触觉刺激，并将此信息传递到中枢神经 系统（CNS）。我们的实验室已经生产出遗传工具，使可视化和功能操纵的 主要LTMR亚型在小鼠，揭示了初级LTMR传入传递高度组织化 关于它们检测到的触摸刺激的性质和位置的信息。然而， 在CNS中建立LTMR连接，以产生机械感觉输入的功能组织 仍然未知。特别是，神经活动在LTMR形态发生、中枢靶向和 突触发生尚未被测试。我提出的研究目标是描述结构和 LTMR神经元的功能发育，并测试活动在建立LTMR神经元的组织模式中的作用。 CNS中的LTMR连接。目标1将使用遗传工具来表征LTMR的获得 形态和中枢靶向模式，以及LTMR与其CNS之间的突触形成 目标的在目标2中，我将使用电生理记录来监测功能反应的成熟 性质，并将产生遗传工具，以调查在LTMR神经活动的作用， 中枢定位和突触发生。总之，我提出的研究将确定如何处理电路， 建立触觉刺激以允许躯体感觉的精细空间和功能组织 在CNS中的表现。了解触摸电路在开发过程中是如何组装的， 旨在促进感觉轴突再生的研究工作， 损伤或疾病，以及设计有效的神经修复术来恢复感觉功能。