Neurobiological Basis for Cold Transduction

描述（由申请人提供）：在周围神经系统中，体感神经元报告的温度范围很广，从有害的热到有害的冷。我们知道不同的神经纤维亚群会对特定的温度阈值做出反应，大概是基于它们表达的热感觉分子。此外，这些神经在检测疼痛、组织损伤刺激方面起着关键作用。我们最近开始了解这些神经纤维是如何通过识别对不同热刺激有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，它们对辣椒素和薄荷醇等化合物的敏感性被识别出来，这些化合物可以模拟不同的心理物理感觉。总的来说，这些热传感器可以检测到我们感知到的广泛温度范围，并为温度的检测提供了分子解释。尽管如此，我们对介导和调节这些热传感器的细胞转导机制的理解仍然有限。因此，我们正在分析表达冷和薄荷醇受体TRPM8的感觉传入，以进一步表征介导冷感觉的转导机制。为此，我们产生了转基因小鼠，在体内可检测到的trpm8阳性感觉神经元中特异性表达荧光标记。通过这个动物模型，我们正在研究冷敏感传入神经的外周投射，天然细胞的冷适应机制，以及这些神经元在体感觉中的体内作用。

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.