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. ? ? ?
