Genetic Mapping of Somatosensory Neural Networks

体感神经网络的遗传图谱

• 批准号: 6907025
• 负责人: David D McKemy
• 金额: $ 22.55万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6907025
• 关键词: afferent nerve; agglutinins; artificial chromosomes; behavior test; cell surface receptors; central neural pathway /tract; diphtheria toxin; dorsal horn; gene expression; genetic mapping; genetic models; genetic promoter element; genetically modified animals; green fluorescent proteins; immunocytochemistry; inflammation; laboratory mouse; membrane channels; model design /development; nerve injury; neural information processing; neurogenetics; pain; plant proteins; somesthetic sensory cortex; afferent nerve; agglutinins; artificial chromosomes; behavior test; cell surface receptors; central neural pathway /tract; diphtheria toxin; dorsal horn; gene expression; genetic mapping; genetic models; genetic promoter element; genetically modified animals; green fluorescent proteins; immunocytochemistry; inflammation; laboratory mouse; membrane channels; model design /development; nerve injury; neural information processing; neurogenetics; pain; plant proteins; somesthetic sensory cortex

DESCRIPTION (provided by applicant): In mammals, the detection of stimuli of a chemical, mechanical, or thermal nature occurs through a complex network of primary and higher-order sensory neurons that make up our somatosensory system. A significant advance in our understanding of somatosensation at the molecular level came from the identification of members of the transient receptor potential (TRP) channel family as the primary detectors of thermal stimuli in peripheral nerves. These "thermosensors" are sensitive over distinct temperature ranges and, in most cases, define discrete populations of sensory neurons. However, how signals evoked by thermal stimuli are interpreted and processed at levels higher than the peripheral afferents, as well as the architecture of the neural networks used to communicate these stimuli is still unclear. The aims of this application are to develop genetic model systems that will enable the mapping of somatosensory neural networks involved in the detection of specific stimulus modalities. These exploratory studies will focus on the recently cloned cold and menthol receptor, CMR1 or TRPM8. We intend to use the TRPM8 transcriptional promoter to specifically express a transneuronal tracer in TRPM8+ peripheral afferent nerves in order to map the neural networks and synaptic connections used by these neurons to communicate temperature centrally. After this animal model has been established, we will then assess for changes in spinal organization of TRPM8 neural networks that may result after the induction of inflammatory or neuropathic pain. We will also assess the physiological relevance of this population of sensory nerves by developing a mouse model in which these cells can be conditionally ablated. The experienced gained from these exploratory studies will be used for future investigations of other thermosensors and will expand our understanding of how we detect and discriminate sensory stimuli.

描述（由申请人提供）：在哺乳动物中，检测化学，机械或热性质的刺激是通过构成我们的体感系统的一级和高阶感觉神经元的复杂网络进行的。我们对分子水平的体质的理解的重大进展来自于将瞬态受体电位（TRP）通道家族的成员鉴定为外周神经中热刺激的主要检测器。这些“热传感器”对不同温度范围很敏感，在大多数情况下，定义了感觉神经元的离散群体。但是，热刺激引起的信号的解释和处理高于外围传入的水平，以及用于传达这些刺激的神经网络的结构尚不清楚。该应用的目的是开发遗传模型系统，以实现参与检测特定刺激方式的体感神经网络的映射。这些探索性研究将集中于最近克隆的冷和薄荷醇受体CMR1或TRPM8。我们打算使用TRPM8转录启动子在TRPM8+外围传入神经中特异性表达跨神经元示踪剂，以绘制这些神经元所用的神经网络和突触连接，以中央进行温度进行通信。建立该动物模型后，我们将评估TRPM8神经网络的脊柱组织的变化，这可能在诱导炎症性或神经性疼痛后可能导致。我们还将通过开发一个可以有条件地消融这些细胞的小鼠模型来评估这种感觉神经的生理相关性。从这些探索性研究中获得的经验丰富的收益将用于对其他热传感器的未来研究，并将扩展我们对我们如何检测和区分感觉刺激的理解。