Peripheral mechanisms of neurotransmission in mammalian touch receptors

项目摘要 触觉使人类的日常行为，包括喂养，导航和社交互动成为可能。的 这项研究的目的是确定哺乳动物编码触摸的外周机制。该项目重点 在默克尔细胞-神经突复合体上，这是在身体部位专门用于精细触摸的温和触摸受体。 机械敏感性默克尔细胞与背根神经节的快速传导传入神经形成突触样接触。 默克尔细胞被认为是通过在常规化学刺激下释放神经递质来激活感觉传入的。 然而，神经传递的分子机制仍然未知。此应用程序的 中心假设是默克尔细胞利用SNARE依赖性囊泡释放单胺能 神经递质来激活感觉传入神经的放电。该假设将使用以下组合进行检验： 活细胞成像、转基因小鼠模型、离体电生理学、药理学和感觉行为 试验.目的1将测试默克尔细胞是否采用SNARE介导的囊泡释放神经递质。目标2将 确定默克尔细胞是否采用单胺能神经传递来激发触觉传入的放电。目的 3将阐明是否单胺能神经传递所需的温柔触摸诱发的行为。拟议 研究将确定突触传递和突触后受体途径的分子机制， 默克尔细胞-神经突复合体。这一知识将使我们理解支配 触觉功能和编码在健康的神经系统。

Project Summary The sense of touch enables everyday human behaviors, including feeding, navigation and social interaction. The goal of this research is to define the peripheral mechanisms that encode touch in mammals. This project focuses on Merkel cell-neurite complexes, which are gentle-touch receptors found in body sites specialized for fine touch. Mechanosensitive Merkel cells form synaptic-like contacts with fast-conducting afferents of dorsal root ganglia. Merkel cells are proposed to activate sensory afferents by neurotransmitter release at conventional chemical synapses, however, the molecular mechanisms of neurotransmission remain unknown. This application’s central hypothesis is that Merkel cells employ SNARE-dependent vesicular release of monoaminergic neurotransmitters to activate firing in sensory afferents. The hypothesis will be tested using a combination of live-cell imaging, transgenic mouse models, ex vivo electrophysiology, pharmacology, and sensory behavioral tests. Aim 1 will test if Merkel cells employ SNARE-mediated vesicle release of neurotransmitter. Aim 2 will determine whether Merkel cells employ monoaminergic neurotransmission to excite firing in tactile afferents. Aim 3 will elucidate if monoaminergic neurotransmission is required for gentle-touch evoked behaviors. The proposed studies will define the molecular mechanisms of synaptic transmission and post-synaptic receptor pathways at the Merkel cell-neurite complex. This knowledge will our understanding of the fundamental principles that govern tactile function and encoding in the healthy nervous system.