CORTICAL REPRESENTATIONS OF COLD

寒冷的皮质表征

基本信息

批准号：
8713041
负责人：
ALISON L BARTH
金额：
$ 21.73万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8713041
关键词：
Address Affective Animal Model Animals Area Brain Cell Nucleus Cerebral cortex Chemicals Clinical Complex Data Disease Dissection Emotional Esthesia FOS gene Foundations Functional Magnetic Resonance Imaging Gene Expression Goals Human Immediate-Early Genes Immunohistochemistry Insula of Reil Knockout Mice Label Lead Learning Ligands Link Mammals Maps Mechanics Mediating Menthol Molecular Molecular Genetics Mus Neocortex Neurons Nociception Nociceptive Stimulus Pain Pain Disorder Parietal Lobe Pathway interactions Patients Peripheral Physiological Play Process Property Receptor Activation Reporter Resolution Rodent Role Route Scientist Sensory Signal Transduction Somatosensory Cortex Spinal Cord Spinal Ganglia Stimulus Stream Stroke Suid Herpesvirus 1 Symptoms Tactile Techniques Temperature Testing Thalamic structure Time Tracer Transgenic Mice Viral Virus base central pain central pain syndrome cold temperature experience heat stimulus in vivo insight knockout gene mimetics neocortical nerve supply particle pressure public health relevance receptive field receptor red fluorescent protein research study response tool two-photon vibration

项目摘要

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.

描述（由申请人提供）：温度和疼痛感觉异常是中风后患者的常见症状，在某些情况下可能导致中枢性疼痛综合征，这是一种使人衰弱的疾病。新皮质回路的可塑性可能发挥重要作用这种病。在这里，我们将使用复杂的分子工具和最先进的记录技术来识别代表小鼠疼痛和温度刺激的主要新皮质区域。实验将集中于 TrpM8 受体介导的冷感。 TrpM8 是 ~10-24o C 温度感觉所需的唯一受体，遗传上缺乏 TrpM8 的动物在该范围内缺乏温度感觉。除了低温之外，表达 TrpM8 的神经元还可以被化学配体薄荷醇兴奋，为特定受体激活提供补充途径。我们的初步数据表明，TrpM8 刺激特异性激活后岛叶中的神经元，并且在 TrpM8 受体敲除小鼠中不存在这种激活。我们将在 fosGFP 转基因小鼠中使用冷刺激或薄荷醇刺激，然后对 fosGFP+ 神经元进行 2 光子靶向体内记录，以确定冷激活神经元的感受野特性。这些实验将为理解新皮质中的疼痛和温度回路如何因经验和疾病而改变奠定重要基础。