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: 9532342
• 负责人: JANET R KEAST
• 金额: $ 45.29万
• 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 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9532342
• 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.

摘要 这个基础性的项目将产生中观和微观的功能解剖图 调节下尿路(LUT)的感觉和自主神经(运动神经元)。神经功能障碍是一种 导致各种基本上难以解决的泌尿系统问题的主要因素，包括过度活跃或活动不足 膀胱、因年龄增长或骨盆手术导致的大小便失禁以及痛性膀胱综合征/间质性膀胱炎。我们 将填补知识空白并克服各种技术障碍，以制定可提供关键 为模拟不同的LUT行为，了解神经调节机制，以及 确定神经调节的非靶点效应。我们将在成年大鼠身上进行这项研究，这种物种 LUT的外周和脊髓电路被最详细地定义，并且与小鼠相比，它们的 更大的尺寸有利于设备的开发。总而言之，这将促进开发新的方法 使这些回路的过度活动或活动不足正常化。男性和女性的目标是：(1) 为了描绘支配膀胱体的不同类别的感觉和自主神经元的功能， 三角区和近端尿路。我们还将映射投射到其中一个以上区域的神经元 (`串音‘)。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投射神经元的rna-seq分析的最新结果 并映射新的功能子类标记。(2)定位感觉神经元的脊髓靶点 支配膀胱体、三角区和近端尿路。使用病毒追踪，我们将绘制和描述 自主神经反射和伤害性感受通路中的二级感觉神经元；我们还将确定 来自两个外围目标的融合。(3)标测生理或非生理因素激活的脊髓神经元。 电诱导清醒大鼠排尿。我们在慢性盆腔神经激活方面的最新进展- 留置导管的清醒动物将与神经激活的标志相结合，详细的表型 激活神经元和病毒追踪。