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

描述（由申请人提供）：我们使用分子遗传学来识别和表征 C 纤维低阈值机械感受器 (C-LTMR)，这是一种 DRG 感觉神经元，被认为有助于损伤引起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-LTMR 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目标，以试图阐明关键的机械敏感和伤害感受回路。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人们知之甚少的神经元群的解剖学特征。为了进一步定义 C-LTMR 回路，我们将这些工具与生理学方法结合起来，以测试背角层 IIiv 的 PKC3 中间神经元是 C-LTMR 的突触后伙伴的假设。最后，我们将生成新的小鼠系来消除成人体内的 C-LTMR，以直接测试 C-LTMR 是否是机械异常性疼痛和毛状皮肤柔软触感的关键介质。总之，这项研究将揭示 C-LTMR 的形态特性，定义 C-LTMR 特异性神经回路，并确定 C-LTMR 在机械感觉和异常性疼痛中的作用。

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.