Mapping brainstem control of urine storage and voiding in conscious mice

绘制清醒小鼠尿液储存和排尿的脑干控制图

• 批准号: 8904046
• 负责人: Mark L. Zeidel
• 金额: $ 33.63万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8904046
• 关键词: Age; Animals; Area; Benign; Biological Neural Networks; Bladder; Bladder Diseases; Boston; Brain; Brain Stem; Central Nervous System Diseases; Conscious; Designer Drugs; Development; Diabetes Mellitus; Disease; Elderly; Electrodes; Functional Imaging; Future; Genetic; Goals; Health; Human; Individual; Institution; Intervention; Knowledge; Lead; Lesion; Light; Link; Lower urinary tract; Maps; Methods; Modality; Modeling; Mus; Neurons; Neurotransmitters; Pathogenesis; Patients; Pharmaceutical Preparations; Physiology; Pontine structure; Population; Rabies virus; Research; Research Personnel; Resource Development; Role; Running; Site; Spinal Cord; Staging; Stress; Symptoms; Synapses; Testing; Therapeutic; Urethra; Urination; Urine; Urologist; Urology; base; cost; effective therapy; graduate student; human subject; improved; insight; lower urinary tract symptoms; magnetic field; mind control; mouse model; nervous system disorder; neural circuit; neuroregulation; new technology; novel; novel diagnostics; novel therapeutics; optogenetics; patient population; programs; public health relevance; receptor; relating to nervous system; response; symposium; tool

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.

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，对此几乎没有可靠和有效的治疗方法。我们缺乏治疗方法，因为我们不了解根本原因，包括大脑控制尿液储存和排尿的紊乱的作用。该项目的总体目标是 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（当前的提案）。该中心是一个资源开发项目，旨在利用最先进的神经图谱方法，包括光遗传学、设计药物独家激活的设计受体 (DREADD) 和狂犬病病毒突触追踪，以确定特定脑桥排尿中心 (PMC) 神经元亚群在尿液储存和排尿中的功能作用。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图的影响。对 PMC 神经元亚群功能的详细了解，以及对其上哪些神经元突触的了解，将为我们小组和其他研究人员在未来几年详细绘制整个过程奠定基础。 控制尿液储存和排尿的神经网络。该丰富项目将侧重于将世界领先的神经生物学家带入良性泌尿学领域，并培养未来中枢神经系统控制尿液储存和排尿的研究人员（包括提案中支持的研究生）。此外，我们将举办研讨会，以帮助识别我们自己的泌尿科医生 波士顿的机构和其他机构可以帮助我们开展人类受试者研究，这将使我们能够向患者扩展我们在小鼠身上开发的见解。