Regional differences in itch transmission

神经系统将不成比例的神经元资源分配给对生物体的生存和繁殖至关重要的感觉信息。例如，手掌的皮肤，特别是手指尖，具有最高密度的触摸传感器，以允许对象识别和操纵。该提案旨在使用瘙痒感知神经回路作为模型系统，以了解哺乳动物神经系统如何在无毛（非毛）皮肤中实现更高的感觉处理灵敏度。PI的小组先前将MrgprC11+神经元鉴定为引起小鼠近端身体和无毛皮肤的瘙痒感觉的主要介质。该项目将研究MrgprC11+神经元的形态和生理特征，以提供对感觉处理区域差异的机械理解。该项目将支持本科生和研究生的培训，包括那些来自科学领域代表性不足群体的学生。该项目还将为高中科学教师提供分析神经元连接的实践经验，并促进高中的神经科学教育。总的来说，这个项目将拓宽我们对瘙痒感觉的科学和社会理解。无毛皮肤的不成比例的中央代表是躯体感觉皮层地图最显著的特征。然而，在躯体感觉回路中，这种有偏见的表征出现在哪里，而扭曲表征背后的分子和细胞基础在很大程度上是未知的。本项目将分析控制不同身体位置的MrgprC11+痒感背根神经节神经元，以研究初级感觉神经元如何对扭曲的皮层表示做出贡献。将采用形态学、转录组学和生理学方法的组合来解决三个具体目标。目的1将确定瘙痒传播的区域差异的形态学基础，以及这在发育过程中是如何建立的。目的2将确定皮肤类型的瘙痒感应神经元的特定生理特性，以实现提高无毛皮肤的敏感性。目的3研究无毛皮肤特异性突触的形成和修剪机制，以促进无毛皮肤的瘙痒传递。产生的结果将加深我们对脊椎动物的疼痛感觉系统的躯体组织的理解。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

The nervous system allocates disproportional neuronal resources to sensory information that are critical for an organism’s survival and reproduction. For example, the skin of the palms of the hands, especially the figure tips, have the highest density of touch sensors to allow object recognition and manipulation. This proposal aims to use the itch-sensing neural circuit as a model system to understand how the mammalian nervous system achieves higher sensitivity of sensory processing in the glabrous (non-hairy) skin. The PI’s group previously identified MrgprC11+ neurons as the main mediator for itch sensation arising from both the proximal body and the glabrous skin of mice. This project will examine the morphological and physiological features of MrgprC11+ neurons to provide a mechanistic understanding of regional differences in sensory processing. The project will support the training of undergraduate and graduate students, including those from underrepresented groups in science. The project will also provide high school science teachers with hands-on experience to analyze neuronal connections and promote neuroscience education in high schools. Overall, this project will broaden our scientific and societal understanding of itch sensation.Disproportional central representation of the glabrous skin is the most striking feature of the somatosensory cortical map. However, where in the somatosensory circuits such biased representations emerge and the molecular and cellular basis underlying the distorted representation are largely unknown. This project will analyze the MrgprC11+ itch-sensing dorsal root ganglia neurons controlling different body locations to investigate how primary sensory neurons contribute to the distorted cortical representation. A combination of morphological, transcriptomic, and physiological approaches will be employed to address three specific aims. Aim 1 will determine the morphological basis of regional differences in itch transmission and how this is established during development. Aim 2 will identify the skin-type specific physiological properties of itch-sensing neurons to achieve heightened glabrous skin sensitivity. Aim 3 will investigate skin-type specific synapse formation and pruning mechanisms to promote itch transmission of the glabrous skin. Results generated will deepen our understanding of the somatotopical organization of the nocifensive sensory system in vertebrates.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.