Understanding functional connectivity of sensory and motor pathways to specific regions of the lower urinary tract.

了解感觉和运动通路与下尿路特定区域的功能连接。

• 批准号: 9920329
• 负责人: JANET R KEAST
• 金额: $ 9.72万
• 依托单位: UNIVERSITY OF MELBOURNE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-28 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920329
• 关键词: Address; Adult; Afferent Neurons; Aging; Anatomy; Animals; Area; Behavior; Biomedical Engineering; Bladder; Bladder Control; Brain; Catheters; Chronic; Clinical; Communities; Conscious; Development; Device or Instrument Development; Elements; Experimental Designs; Female; Foundations; Ganglia; Human; Incontinence; Injury; Interstitial Cystitis; Ion Channel; Knowledge; Label; Lower urinary tract; Maps; Methods; Microscopic; Micturition Reflex; Modality; Modeling; Motor; Motor Neurons; Motor Pathways; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Nerve; Neural Pathways; Neuroanatomy; Neurobiology; Neuronal Dysfunction; Neurons; Nociception; Nociceptors; Ontology; Operative Surgical Procedures; Organ; Outcome; Overactive Bladder; Pain; Pathway interactions; Pelvic Pain; Pelvis; Peripheral; Peripheral Nerves; Pharmacology; Phenotype; Physiological; Population; Rattus; Recovery; Reflex action; Research Support; Sensory; Site; Spinal; Spinal Cord; Striated Muscles; System; Technology; Time; Tissues; Urethra; Urologic Diseases; Viral; Visceral pain; annotation system; autonomic nerve; autonomic reflex; base; bladder trigone; career; clinical translation; experience; injured; male; nerve supply; neuroregulation; new technology; new therapeutic target; novel marker; relating to nervous system; skills; transcriptome sequencing; urologic

ABSTRACT This foundational project will produce mesoscopic and microscopic functional anatomical maps of the sensory and autonomic (motor) neurons that regulate the lower urinary tract (LUT). Neural dysfunction is a major contributor to diverse, largely intractable urological problems, including overactive or underactive bladder, incontinence due to ageing or pelvic surgery, and painful bladder syndrome/interstitial cystitis. We will fill knowledge gaps and overcome diverse technical roadblocks to develop maps that provide a critical foundation for modeling different LUT behaviors, understanding neuromodulatory mechanisms, and determining off-target effects of neuromodulation. We will conduct this study in adult rats, the species where the peripheral and spinal circuitry of the LUT is defined in the most detail and, compared with mice, their larger size facilitates development of devices. Together, this will facilitate development of new methods for normalizing over- or underactivity in these circuits. The aims to be addressed in males and females are: (1) To map functionally distinct classes of sensory and autonomic neurons that innervate the bladder body, trigone and proximal urethra. We will also map neurons that project to more than one of these regions (`cross-talk'). In addition to known functional markers of sensory and autonomic neural subtypes, we will use the latest outcomes of our RNA-seq analyses of retrogradely labeled bladder-projecting neurons to define and map new markers of functional subclasses. (2) To map the spinal targets of sensory neurons innervating the bladder body, trigone and proximal urethra. Using viral tracing we will map and characterize second order sensory neurons in autonomic reflex and nociceptive pathways; we will also identify sites of convergence from two peripheral targets. (3) To map the spinal neurons activated by physiologically- or electrically-induced voiding in conscious rats. Our recent advance of activating pelvic nerves in chronically- catheterized conscious animals will be combined with markers of neural activation, detailed phenotyping of activated neurons and viral tracing.

抽象的 这个基础项目将产生介观和显微镜功能解剖图的 调节下尿路（LUT）的感觉和自主（运动）神经元。神经功能障碍是 导致多种多样的，棘手的泌尿外科问题的主要贡献者，包括活动过度或无效 膀胱，由于衰老或盆腔手术而导致的动荡，膀胱综合征/间质性膀胱炎。我们 将填补知识空白并克服多样化的技术障碍，以开发地图，从而提供关键 建模不同的LUT行为的基础，了解神经调节机制和 确定神经调节的脱靶作用。我们将在成年大鼠中进行这项研究，该物种 LUT的外围和脊柱电路是最细节定义的，与小鼠相比 较大的尺寸有助于设备的开发。一起，这将有助于开发新方法 在这些电路中归一化或不足。在男性和女性中要解决的目的是：（1） 为了绘制功能上不同的感觉和自主神经元的支配，使膀胱支配， Trigone和近端尿道。我们还将映射将这些项目投影到这些区域中的一个以上的神经元 （“串扰”）。除了已知的感觉和自主神经亚型的功能标记外，我们还将使用 我们对逆行标记的膀胱预测神经元的RNA-seq分析的最新结果以定义 并映射功能子类的新标记。 （2）绘制感觉神经元的脊柱靶标 支配膀胱身体，三角形和近端尿道。使用病毒跟踪，我们将映射和表征 自主反射和伤害感受途径中的二阶感觉神经元；我们还将确定 来自两个外围目标的收敛。 （3）绘制由生理学或 有意识大鼠的电诱导的空隙。我们最近在慢性上激活骨盆神经的进步 导管意识的动物将与神经激活的标记结合在一起，详细的表型 活化的神经元和病毒痕迹。