Mapping brainstem control of urine storage and voiding in conscious mice

描述（由申请人提供）：下尿路症状和相关紊乱是一个主要的健康问题，几乎没有可靠和有效的治疗方法。我们缺乏治疗，因为我们不了解根本原因，包括大脑控制尿液储存和排泄的干扰作用。的总体目标 PI将开发小鼠作为LUTS模型，利用小鼠遗传学（PI当前的P20）和绘制小鼠神经回路的新技术（当前提案）。该中心是一个资源开发项目，旨在使用最先进的神经映射方法，包括光遗传学，设计师受体独家激活的设计师药物（DREADDs）和狂犬病病毒突触追踪，以确定特定的脑桥排尿中心（PMC）神经元亚群在尿液储存和排泄中的功能作用。将确定激活或沉默PMC神经元亚群对自发排尿和有意识膀胱测压的影响。对PMC神经元亚群功能的详细了解，沿着对哪些神经元突触在其上的理解，将在未来几年为我们小组和其他人的研究人员详细绘制整个神经元的结构奠定基础。 控制尿液储存和排泄的神经网络。丰富计划将集中在良性泌尿学领域的世界领先的神经生物学家，并发展未来的研究人员在中枢神经系统控制尿液储存和排尿（包括研究生支持的建议。此外，我们将举办研讨会，以帮助确定泌尿科医生在我们自己的 研究机构和波士顿的其他机构可以帮助我们开发人类受试者研究，这将使我们能够将我们在小鼠中开发的见解扩展到患者。

DESCRIPTION (provided by applicant): Lower urinary tract symptoms and related disturbances represent a major health problem, for which there are few reliable and effective treatments. We lack therapies because we do not understand the underlying causes, including the role of disturbances in the brain control of urine storage and voiding. The overall goal of the PI is to develop the mouse as a model of LUTS, exploiting mouse genetics (the PI's current P20) and new technologies for mapping neural circuits in mice (the current proposal). The Center is a Resource Development Project, which seeks to use state of the art neural mapping methods, including optogenetics, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), and rabies virus synapse tracing, to determine the functional roles of specific pontine micturition center (PMC) neuron subpopulations in urine storage and voiding. The impact of activating or silencing PMC neuron subpopulations on spontaneous voiding and conscious cystometrograms will be determined. Detailed knowledge of the function of PMC neuron subpopulations, along with an understanding of which neurons synapse on them will set the stage in future years for investigators in our group and others to map out in detail the entire neural network controlling urine storage and voiding. The enrichment program will focus on bringing to the field of benign urology world leading neurobiologists, and developing future investigators in CNS control of urine storage and voiding (including the graduate student supported in the proposal. In addition, we will run symposia to help identify urologists at our own institution and others in Boston who can help us to develop human subjects studies which will allow us to extend to patients the insights which we are developing in mice.