Central Circuits of Peripheral Sensory Neurons

描述（由申请人提供）：初级感觉神经元将疼痛和非疼痛的热刺激和机械刺激从周围传递到脊髓。生理学研究已经确定了初级感觉神经元的许多功能不同的亚型（根据它们对刺激的反应、髓鞘形成程度和神经支配模式来定义），但每种类型如何影响行为仍未得到很好的理解。对每个种群的分子标记的鉴定现在允许使用更强大的遗传方法来识别功能重要的分子，绘制它们的中心连接并确定它们在体感知觉中的作用。在这项拨款申请中，我们利用我们鉴定的独特分子标记和这些新的强大工具来阐明由无髓鞘低阈机械受体（C-LTMRs）激活的中央电路。这些细胞被认为传递愉悦的触觉和由神经损伤引起的持续的机械性疼痛。我们还将利用我们开发的新的转基因报告系来识别其他功能定义的初级感官群体的分子标记。标记基因将使我们能够解决躯体感觉生物学的许多方面，这在以前是不可行的。这些新方法对于理解躯体感觉处理的基本原理及其在正常条件下和慢性疼痛状态下与感知的关系是绝对必要的。

DESCRIPTION (provided by applicant): Primary sensory neurons transmit painful and non-painful thermal and mechanical stimuli from the periphery to the spinal cord. Physiological studies have identified a number of functionally distinct subtypes of primary sensory neurons (defined by their response to stimuli, degree of myelination and innervation pattern), but how each type contributes to behavior is still not well understood. The identification of molecular markers for each population is now permitting the use of more powerful genetic approaches to identify functionally important molecules, map their central connectivity and determine their role in somatosensory perception. In this grant proposal, we take advantage of a unique molecular marker we identified and these new powerful tools to elucidate the central circuitry activated by unmyelinated low threshold mechanoreceptors (C-LTMRs). These cells are thought to transmit pleasant touch and the persistent mechanical pain that results from nerve injury. We will also take advantage of a new transgenic reporter line we developed to identify molecular markers for additional functionally defined primary sensory populations. Marker genes will allow us to address many aspects of somatosensory biology that were previously not feasible. These new approaches are absolutely essential for understanding the fundamental principles of somatosensory processing and its relation to perception under normal conditions and in chronic pain states.