Anatomical, physiological, and behavioral correlates of a C-LTMR circuit

C-LTMR 回路的解剖学、生理学和行为相关性

• 批准号: 8803905
• 负责人: Victoria Eugenia Guadalupe Abraira
• 金额: $ 5.04万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-29 至 2014-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8803905
• 关键词: Anatomical; physiological; behavioral; correlates; LTMR

DESCRIPTION (provided by applicant): We have used molecular genetics to identify and characterize the C-fiber low threshold mechanoreceptor (C- LTMR), a DRG sensory neuron proposed to contribute to injury-induced touch hypersensitivity and the affective, or emotional, component of touch. We propose to assess the in vivo functions of C-LTMRs in adult mice, their morphologies, and their postsynaptic targets in the dorsal horn in an attempt to elucidate key mechanosensitive and nociceptive circuits. We propose to characterize the anatomical features of this poorly understood neuronal population at single cell resolution using newly developed mouse molecular-genetic tools. To further define a C-LTMR circuit we will couple these tools with physiological approaches to test the hypothesis that PKC3+ interneurons of dorsal horn lamina IIiv are post-synaptic partners of C-LTMRs. Finally, we will generate new mouse lines to ablate C-LTMRs in the adult to directly test whether C-LTMRs are key mediators of mechanical allodynia and hairy skin soft touch. Together, this research will reveal the morphological properties of C-LTMRs, define a C-LTMR-specific neural circuit, and establish the role for C- LTMRs in mechanosensation and allodynia.

描述（由申请人提供）：我们已经使用分子遗传学来鉴定和表征C-纤维低阈值机械感受器（C-LTMR），这是一种DRG感觉神经元，被认为有助于损伤诱导的触摸超敏反应和触摸的情感或情绪成分。我们建议评估C-LTMRs在成年小鼠体内的功能，它们的形态，以及它们在背角的突触后靶点，试图阐明关键的机械敏感性和伤害性回路。我们建议使用新开发的小鼠分子遗传学工具，以单细胞分辨率来表征这种知之甚少的神经元群体的解剖特征。为了进一步定义C-LTMR电路，我们将这些工具与生理方法相结合，以测试背角板IIiv的PKC 3+中间神经元是C-LTMR的突触后伙伴的假设。最后，我们将产生新的小鼠品系来消融成年C-LTMR，以直接测试C-LTMR是否是机械性异常性疼痛和多毛皮肤柔软触感的关键介质。总之，这项研究将揭示C-LTMR的形态学特性，定义C-LTMR特异性神经回路，并建立C-LTMR在机械感觉和异常性疼痛中的作用。