CORTICAL REPRESENTATIONS OF COLD

描述（由申请人提供）：体温和疼痛感觉异常是中风后患者的常见症状，在某些情况下可导致中枢性疼痛综合征，这是一种使人衰弱的疾病。新皮层回路的可塑性可能在以下方面发挥重要作用： 这种疾病。在这里，我们将使用复杂的分子工具和国家的最先进的记录技术，以确定主要的新皮质区代表疼痛和温度刺激的小鼠。实验将集中于TrpM 8受体介导的冷感觉。TrpM 8是在~10- 24 ° C温度范围内产生热感觉所需的唯一受体，缺乏TrpM 8基因的动物在这个温度范围内缺乏温度感觉。除了低温，TrpM 8表达神经元还受到化学配体薄荷醇的刺激，为特异性受体激活提供了补充途径。我们的初步数据表明，TrpM 8刺激特异性激活后岛叶的神经元，而这种激活在TrpM 8受体敲除小鼠中不存在。我们将在fosGFP转基因小鼠中使用冷刺激或薄荷醇刺激，然后通过fosGFP+神经元的2光子靶向体内记录来确定冷激活神经元的感受野特性。这些实验将为理解新皮层中的疼痛和温度回路如何被经验和疾病改变奠定关键基础。

DESCRIPTION (provided by applicant): Abnormal temperature and pain sensation is a common symptom of patients after stroke, and in some cases can lead to central pain syndrome, a debilitating disorder. Plasticity in neocortical circuits may play an important role in this disease. Here we will use sophisticated molecular tools and state-of-the-art recording techniques to identify the primary neocortical area representing pain and temperature stimuli in mice. Experiments will focus on cold sensation mediated by the TrpM8 receptor. TrpM8 is the sole receptor required for thermal sensation from ~10-24o C, and animals genetically lacking TrpM8 have a lack of temperature sensation in this range. In addition to cold temperature, TrpM8-expressing neurons are excited by the chemical ligand menthol, offering complementary routes for specific receptor activation. Our preliminary data indicate that TrpM8 stimulation specifically activates neurons in the posterior insula and that this activation is absent in TrpM8 receptor knock-out mice. We will use cold- or menthol stimulation in fosGFP transgenic mice followed by 2-photon targeted in vivo recordings of fosGFP+ neurons to determine the receptive field properties of cold-activated neurons. These experiments will lay a critical foundation for understanding how pain and temperature circuitry in the neocortex can be modified by experience and disease.