Regional differences in itch transmission

瘙痒传播的区域差异

• 批准号: 2334697
• 负责人: Liang Han
• 金额: $ 55万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2334697&HistoricalAwards=false
• 关键词: Regional; differences; itch; transmission

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.

神经系统将不成比例的神经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（尤其是指尖）具有最高密度的触摸传感器，可以进行物体识别和操作。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（无毛）皮肤中实现更高的感觉处理灵敏度。 MrgprC11+ 神经元作为小鼠近端身体和无毛皮肤产生瘙痒感的主要介质，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制理解。培训本科生和研究生，包括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连接和促进高中神经科学教育的实践经验。总体而言，该项目将拓宽我们对瘙痒感的科学和社会理解。无毛皮肤的不成比例的中央表征是体感皮质图最显着的特征，然而，在体感回路中出现这种偏差的表征以及分子和神经元。扭曲表征背后的细胞基础在很大程度上是未知的，该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促进扭曲的皮质表征将采用形态学、转录组学和生理学方法的结合来解决三个具体目标，目标 1 将确定瘙痒传播的区域差异的形态学基础，以及目标 2 在发育过程中如何确定这一点。目标3将研究皮肤类型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。加深我们对脊椎动物伤害感觉系统的体位组织的理解。该奖项反映了 NSF 的法定使命，并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，被认为值得支持。