High resolution mapping of lower urinary tract innervation during development

发育过程中下尿路神经支配的高分辨率绘图

基本信息

批准号：
8730770
负责人：
JANET R KEAST
金额：
$ 10.8万
依托单位：
UNIVERSITY OF MELBOURNE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8730770
关键词：
Address Adult Afferent Neurons Anatomy Atlases Axon Behavior Bilateral Birth Bladder Brain Chemicals Conscious Cystitis Databases Development Disease Event Excision Female Foundations Future Ganglia Genitourinary system Goals Growth Health Immunohistochemistry In Situ Hybridization Injury Intestines Lower urinary tract Malignant Neoplasms Maps Methods Molecular Motor Motor Neurons Mus Mutation Natural regeneration Nerve Nervous system structure Neurons Operative Surgical Procedures Organ Outcome Overactive Bladder Pattern Pelvic Pain Pelvis Peripheral Nervous System Population Process Prostatectomy Proteins Puberty Research Personnel Resolution Rodent Role Sensory Sex Behavior Solutions Source Spinal Spinal Ganglia System Time Tissues Urethra Urination afferent nerve autonomic nerve cell type chemical fingerprinting design injured knowledge base male mind control molecular marker nerve supply new growth novel novel strategies postnatal prenatal receptor receptor expression reproductive response to injury urinary bladder neck

项目摘要

DESCRIPTION (provided by applicant): The primary behaviors of the mature lower urinary tract (LUT) - storage and voiding depend on a functional nervous system. Development of these circuits in the prenatal period is poorly understood. Postnatal, there is a dramatic transition frm the immature situation where voiding is "automatic", i.e., not controlled by brain-driven processes, to the healthy mature system where filling triggers a conscious need to void, but micturition is determined voluntarily at an appropriate time and place. Around puberty, further changes occur to coordinate bladder, bowel and sexual activity. Many events occur in the nervous system over these periods, although the cellular loci and molecular mechanisms have not been defined. The goals of this molecular anatomy GUDMAP Atlas Project are to map (i) the detailed temporal and spatial profiles of axon connections that form with the mouse lower urinary tract during pre- and postnatal periods, and (ii) the expression of factors/receptors that may initiate and sustain these connections. The project will use robust neuroanatomical methods including tract tracing, immunohistochemistry and in situ hybridization to address three aims: (1) To map the terminal fields of key functional and chemical classes of sensory and motor axons within the mouse LUT during development and postnatal maturation; (2) To define the structural and chemical "fingerprint" of sensory and autonomic neurons innervating the mouse LUT during this period; (3) To map the cellular source of neurotrophic and guidance factors that determine connectivity between nerves and the mouse LUT. Constructing this knowledge base is essential to understand how these connections form (or fail to form) and the mechanisms that may sustain or modulate them in health, disease or injury states. Establishing a structural and chemical fingerprint of developing and mature bladder neurons will also allow researchers to interpret many of the current expression patterns in the GUDMAP database. More broadly, the outcomes will promote understanding of these developing and maturing circuits and provide a strong foundation to analyze plasticity and injury responses in the developing and adult urogenital system.

描述（由申请人提供）：成熟的下尿路（LUT）的主要行为——储存和排尿取决于功能性神经系统。人们对这些回路在产前时期的发育知之甚少。出生后，从不成熟的情况（排尿是“自动的”，即不受大脑驱动的过程控制）到健康成熟的系统（充盈触发有意识的排尿需要，但排尿是在适当的时间自愿决定）发生了戏剧性的转变。时间和地点。青春期前后，膀胱、肠道和性活动的协调会发生进一步的变化。尽管细胞位点和分子机制尚未确定，但在这些时期神经系统中发生了许多事件。该分子解剖学 GUDMAP 图集项目的目标是绘制 (i) 产前和产后期间与小鼠下尿路形成的轴突连接的详细时间和空间轮廓，以及 (ii) 因子/受体的表达可以启动并维持这些连接。该项目将使用强大的神经解剖学方法，包括束追踪、免疫组织化学和原位杂交来实现三个目标：（1）绘制发育和出生后成熟过程中小鼠LUT内感觉和运动轴突关键功能和化学类别的末端区域图； (2) 定义该时期支配小鼠LUT的感觉和自主神经元的结构和化学“指纹”； (3) 绘制决定神经和小鼠 LUT 之间连接的神经营养和引导因子的细胞来源。构建这个知识库对于理解这些连接如何形成（或无法形成）以及在健康、疾病或受伤状态下维持或调节它们的机制至关重要。建立发育和成熟膀胱神经元的结构和化学指纹也将使研究人员能够解释 GUDMAP 数据库中的许多当前表达模式。更广泛地说，这些结果将促进对这些发育和成熟回路的理解，并为分析发育中和成人泌尿生殖系统的可塑性和损伤反应提供坚实的基础。