Neurobiological Basis for Cold Transduction

描述(申请人提供)：在外周神经系统中，体感神经元报告的温度范围很广，从有害的高温到有害的寒冷。我们知道，神经纤维的不同亚群会对特定的温度阈值做出反应，这可能是基于它们表达的温度感觉分子。此外，这些神经在检测疼痛、组织破坏性刺激方面起着关键作用。我们最近已经开始掌握这些神经纤维是如何通过识别对不同热刺激做出反应的分子来检测温度的。这些分子是瞬时受体电位(Trp)通道家族的成员，通过它们对辣椒素和薄荷醇等化合物的敏感性来识别，这些化合物模仿不同的心理物理感觉。总而言之，这些温度传感器可以检测到我们感知到的广泛温度范围，并为温度是如何检测到的提供了分子解释。尽管如此，我们对调节和调节这些温度传感器的细胞转导机制的了解仍然有限。因此，我们正在分析表达寒冷和薄荷醇受体TRPM8的感觉传入，以进一步描述介导寒冷感觉的传导机制。为此，我们产生了转基因小鼠，它们在体内可检测到的TRPM8阳性感觉神经元中特异地表达荧光标记。通过这个动物模型，我们正在研究冷敏感传入的外周投射，冷适应在天然细胞中的机制，以及这些神经元在体内在躯体感觉中的作用。

DESCRIPTION (provided by applicant): In the peripheral nervous system, somatosensory neurons report a wide range of temperatures, from noxious heat to noxious cold. We know that distinct subsets of nerve fibers will respond to specific temperature thresholds, presumably based upon the thermosensory molecules they express. Moreover, these nerves are key players in the detection of painful, tissue damaging stimuli. We have recently begun to grasp how these nerve fibers detect temperature due to the identification of molecules that respond to distinct thermal stimuli. These molecules, members of the transient receptor potential (TRP) channel family, were identified by their sensitivity to compounds, such as capsaicin and menthol, which mimic distinct psychophysical sensations. Taken together, these thermosensors can detect the broad range of temperatures we perceive and provides a molecular explanation for how temperature is detected. Nonetheless, our understanding of the cellular transduction mechanisms that mediate and regulate these thermosensors remains limited. Therefore, we are analyzing the sensory afferents expressing the cold and menthol receptor, TRPM8, to further our characterization of the transduction mechanisms mediating cold sensation. To this end, we have generated transgenic mice that express a fluorescent label specifically in TRPM8-positive sensory neurons that is detectable in vivo. With this animal model, we are investigating the peripheral projections of cold-sensitive afferents, the mechanisms of cold adaptation in native cells, and the in vivo role of these neurons in somatosensation.