Correlation of Urinary Bladder Afferent Activity and Function in Awake Mice

说明（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尚不清楚，在功能失调的膀胱中也知之甚少。在这项提议中，我们寻求发展一种新的，长期的细胞外记录技术，并使用这种方法记录麻醉和清醒小鼠的膀胱神经活动。我们将利用这种技术来阐明感觉信号在正常小鼠和膀胱病理小鼠的排尿调节中的作用。我们将通过手术将记录电极植入体内神经节后膀胱神经，并通过记录同一只小鼠在麻醉状态下和麻醉解除后清醒状态下的膀胱神经活动来证明麻醉显著降低了膀胱神经活动。与盆腔神经和胃下神经的记录不同，节后膀胱神经仅支配膀胱，因此神经记录只包含与膀胱有关的信号。通过切断记录电极的远端或近端记录神经，我们可以选择性地只记录传出或传入活动。通过这种方法，我们可以确定感觉信号和效应器信号在整个神经活动中的比例。在没有麻醉或神经功能障碍的情况下，清醒小鼠的记录将大大增加我们对膀胱正常生理感觉活动的认识。为了研究病理条件下膀胱神经活动的变化，我们将使用一个完善的，手术诱导的部分膀胱流出梗阻小鼠模型。该模型模拟了老年男性良性前列腺增生的临床情况。这些研究将确定功能失调、过度活跃的膀胱的传入和传出变化。神经活动的记录将与使用清醒小鼠膀胱测容术同时研究膀胱功能相结合。这种强大的技术组合将为膀胱充盈和排尿过程中膀胱压力和传入神经活动之间的关系提供关键信息。这些研究将阐明感觉神经和效应神经活动在正常和病理膀胱中的基本作用。清醒小鼠传入活动与膀胱功能之间的关系的清晰理解将阐明神经信号和膀胱收缩的基本关系，这可能有助于识别新的信号模式，这可能是开发针对膀胱病理的新治疗方法的有用靶点。

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.