Correlation of Urinary Bladder Afferent Activity and Function in Awake Mice

描述(申请人提供)：膀胱的功能是储存和排出尿液。这些看似简单的过程需要神经系统和收缩元素的复杂整合和协调。这些过程在正常动物中还不是很清楚，在功能失调的尿囊中也很少被理解。在这项建议中，我们寻求开发一种新的、长期的细胞外记录技术，并使用这种方法来记录麻醉和清醒小鼠的膀胱神经活动。我们将使用这项技术来阐明感觉信号在正常小鼠和膀胱病变小鼠排尿调节中的作用。我们将在体内通过外科手术将记录电极植入节后膀胱神经，并显示麻醉通过记录麻醉下和麻醉移除后清醒状态下的同一小鼠的膀胱神经活动显著降低。与骨盆和腹下神经的记录不同，节后膀胱神经只支配膀胱，因此神经记录只包含与膀胱有关的信号。通过切断记录电极远端或近端的记录神经，我们可以选择性地只记录传出或传出活动。通过这种方式，我们可以确定感觉和效应器信号在总神经活动中的比例。在没有麻醉或神经功能障碍的情况下，从清醒的小鼠身上进行记录将大大增加我们对膀胱正常、生理感觉活动的了解。为了研究病理条件下膀胱神经活动的变化，我们将使用一种成熟的、手术诱导的部分膀胱流出道梗阻的小鼠模型。这个模型模拟了在老年男性中常见的良性前列腺增生症的临床情况。这些研究将确定功能失调、过度活跃的膀胱的传入和传出改变。神经活动的记录将与使用清醒的小鼠膀胱测定术同时研究膀胱功能相结合。这一强大的技术组合将提供有关膀胱充盈和排尿过程中膀胱压力和传入神经活动之间关系的关键信息。这些研究将阐明感觉神经和效应器神经活动在正常和病理尿囊中的基本作用。清楚地了解清醒小鼠的传入活动与膀胱功能之间的关系将有助于阐明神经信号与膀胱收缩的基本关系，这可能有助于识别新的信号模式，为旨在治疗膀胱病理的新疗法的开发提供有用的靶点。

DESCRIPTION (provided by applicant): The function of the urinary bladder is to store and eliminate urine. These seemingly simple processes require a complex integration and coordination of nervous system and contractile elements. These processes are not well understood in normal animals and are poorly understood in dysfunctional urinary bladders. In this proposal we seek to develop a novel, long-term extracellular recording technique and use this methodology to record urinary bladder nerve activity from anesthetized and awake mice. We will use this technique to elucidate the role of sensory signals in regulating micturition in normal mice and in mice with bladder pathology. We will surgically implant the recording electrode onto the postganglionic bladder nerve 'in'vivo-and show that anesthesia significantly decreases bladder nerve activity by recording from the same mouse under anesthesia and in the awake state after anesthesia has been removed. Unlike recordings from pelvic and hypogastric nerves, the postganglionic bladder nerves innervate only the urinary bladder, so the nerve recordings contain only signals related to the bladder. We can selectively record only efferent or afferent activity by severing the recording nerve distal or proximal to the recording electrode. In this way we can determine the proportion of sensory and effector signals to the total nerve activity. Recording from awake mice will substantially increase our knowledge of normal, physiological sensory activity in the urinary bladder in the absence of anesthesia or nerve dysfunction. To study changes in bladder nerve activity under pathological conditions, we will use a well established, surgically-induced mouse model of partial bladder outflow obstruction. This model mimics the clinical condition of benign prostatic hyperplasia often found in older men. These studies will identify afferent and efferent changes in dysfunctional, overactive, urinary bladders. Recordings of nerve activity will be combined with simultaneous studies of bladder function using awake mouse cystometry. This powerful combination of techniques will provide key information on the relationship between bladder pressure and afferent nerve activity during bladder filling and micturition. These studies will elucidate the fundamental role of sensory and effector nerve activity in normal and pathological urinary bladders. A clear understanding of the relationship between afferent activity with bladder function in awake mice will elucidate fundamental relationships of nerve signaling and bladder contraction which may help identify novel signaling patterns that could be useful targets for the development of novel treatments aimed at treating bladder pathology.