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鉴定和表征C-纤维低阈机械受体（C- LTMR），这是一种DRG感觉神经元，被认为与损伤诱导的触觉超敏反应和触觉的情感成分有关。我们建议评估成年小鼠c - ltmr的体内功能，它们的形态和它们在背角的突触后靶点，以试图阐明关键的机械敏感和伤害感觉回路。我们建议在单细胞分辨率下使用新开发的小鼠分子遗传学工具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，我们将把这些工具与生理学方法结合起来，以验证背角iii层PKC3+中间神经元是C-LTMR突触后伙伴的假设。最后，我们将生成新的小鼠系，在成人中消融C-LTMRs，直接测试C-LTMRs是否是机械性异常性痛和毛状皮肤软触的关键介质。本研究将揭示C- ltmr的形态学特征，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.