Mapping brainstem control of urine storage and voiding in conscious mice

描述(申请人提供)：下尿路症状和相关障碍是一个主要的健康问题，几乎没有可靠和有效的治疗方法。我们缺乏治疗方法，因为我们不了解潜在的原因，包括大脑对尿液储存和排尿的控制障碍所起的作用。该计划的总体目标 PI将开发小鼠作为LUTS的模型，利用小鼠遗传学(PI目前的P20)和在小鼠中映射神经回路的新技术(目前的提议)。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、由设计药物(DREADD)独家激活的设计者受体(DREADD)和狂犬病病毒突触跟踪，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尿中的功能作用。激活或沉默PMC神经元亚群对自发排尿和有意识的膀胱测速图的影响将被确定。对PMC神经元亚群功能的详细了解，以及对它们上哪些神经元突触的理解，将为我们小组的研究人员和其他人在未来几年详细绘制整个 控制尿液储存和排尿的神经网络。该项目将致力于将世界领先的神经生物学家带入良性泌尿外科领域，并培养未来在中枢神经系统控制尿液储存和排尿方面的研究人员(包括提案中支持的研究生)。此外，我们将举办座谈会，帮助确定我们自己的泌尿科医生 波士顿的机构和其他人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老鼠身上开发的洞察力扩展到患者身上。

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.