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

基本信息

批准号：
8546523
负责人：
Victoria Eugenia Guadalupe Abraira
金额：
$ 0.52万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-29 至 2013-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8546523
关键词：
Ablation Acute Address Adult Affective Afferent Neurons Alkaline Phosphatase Animals Behavior Behavioral Behavioral Paradigm Biological Assay Brain C Fiber Candidate Disease Gene Cells Code Complex Data Development Diphtheria Toxin Disease Emotional Esthesia Exhibits Future Genes Germ-Line Mutation Goals Hair follicle structure Human Hypersensitivity Immunohistochemistry Individual Injection of therapeutic agent Injury Interneurons Knock-out Label Lead Light Mechanics Mechanoreceptors Mediating Mediator of activation protein Modality Molecular Molecular Genetics Morphology Mus Neurons Nociception Pain Pathway interactions Perception Peripheral Physiological Physiology Population Process Property Research Resolution Role Sensory Signal Transduction Skin Slice Stimulus Stretching Surface Synapses Tail Temperature Testing Tissues Touch sensation Tyrosine 3-Monooxygenase allodynia base cell type chronic pain design diphtheria toxin receptor dorsal horn grasp in vivo interdisciplinary approach mature animal mechanical allodynia neural circuit postsynaptic research study response social somatosensory therapeutic target tool vibration

项目摘要

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，提议有助于损伤诱导的触摸高度和情感或情感，情感，触摸的成分。我们建议评估成年小鼠中C-LTMR的体内功能，它们的形态及其后角中的突触后靶标的体内功能，以阐明钥匙敏感和伤害性电路。我们建议使用新开发的小鼠分子遗传学工具在单细胞分辨率下在单细胞分辨率下对这种不理理解的神经元种群的解剖学特征进行表征。为了进一步定义C-LTMR电路，我们将将这些工具与生理方法相结合，以检验以下假设：背角lamina IIIV的PKC3+中间神经元是C-LTMR的突触后伴侣。最后，我们将生成新的小鼠线以在成年人中消除C-LTMR，以直接测试C-LTMR是否是机械异常性异常和毛茸茸的皮肤柔软触摸的关键介体。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，并确定C-LTMR在机械敏和异肌中的作用。