Minority Predoctoral Fellowship Program

描述（由申请人提供）：在哺乳动物中，P2X受体被发现存在于外周伤害感觉神经元上，与感觉有关。在鱼类中，P2X受体的一个子集被发现定位在一个叫做罗洪-比尔德神经元的主要感觉神经元上。这种细胞类型是胚胎斑马鱼触摸诱发逃避反应的主要介质。通过利用这种动态动物模型来研究哺乳动物的类似感觉现象，可以获得更多暗示P2X受体参与感觉通路的直接证据。为了阐明P2X受体是否介导了鱼类这种行为背后的机械感觉机制，将进行直接解决P2X受体功能的研究。通过使用转基因鱼、morpholino技术和钙指示剂，我们将证明P2X受体是鱼逃避行为背后的机械感觉机制的绝对必要组成部分。通过在该动物模型中直接暗示P2X受体参与感觉，可以更好地了解哺乳动物的感觉。最终，在像Causalgia和风湿性关节炎这样的人类疾病中，指向P2X受体的直接证据将有助于药物的发现。

DESCRIPTION (provided by applicant): P2X receptors in mammals have been found on peripheral nociceptive sensory neurons and are implicated in sensation. In the fish, a subset of P2X receptors has been found to be localized to a primary sensory neuron called the Rohon-Beard neuron. This cell type is the primary mediator of the touch-evoked escape response in the embryonic zebrafish. By utilizing this dynamic animal model to study a similar phenomenon to sensation in mammals, more direct evidence implicating P2X receptors in sensory pathways can be achieved. To elucidate if P2X receptors mediate the mechanosensory mechanism that underlies this behavior in the fish, studies directly addressing P2X receptor function will be conducted. Through the use of transgenic fish, morpholino technology and calcium indicators, we will demonstrate that P2X receptors are an absolutely necessary component to the mechanosensory mechanism that underlies the escape behavior in the fish. By directly implicating P2X receptors in sensation in this animal model, a better understanding of sensation in the mammal can be gleaned. Ultimately, in human conditions like Causalgia and Rheumatoid Arthritis, direct evidence pointing to P2X receptors will aid in drug discovery.