Disorders of the bladder are common in female of all ages and these disorders may be manifested during pregnancy, after childbirth or menopause. Continence and voiding are dependent on the functional integration and coordination ladder and urethral mechanisms. These urogenital mechanisms depend not only on the mechanical properties of the lower urinary tract but also on neural inputs that arise jam the spinal cord and brain. The spinal cord circuits controlling bladder and urethral reflexes are modulated by supraspinal neurons. Previous work has focused on the peripheral and spinal control of bladder function. Fewer studies have examined the reciprical activation and inhibition of bladder and urethral mechanisms by the CNS. Spinal cord circuits controlling detrusor contractions are regulated by neurons in the pontine micturition center in the lateral tegmental field of the pons. These circuits are in turn modulated by supraspinal inputs. The majority of studies examining the CNS control of micturition have used electrical stimulation and lesion techniques. These methods do not distinguish fibers from cell bodies. The present proposal seeks to examine the CNS neurons and pathways that mediate bladder and urethral activity such that they might act reciprocally under normal conditions to maintain continence in the female. A coordinated series of anatomical and physiological experiments will be performed to identify the CNS circuits that modulate bladder and urethral reflexes in the female rat. Brain sites which project to the bladder (base and dome) and urethra (external urethral sphincter and urethra) will be identified by the transneuronal tracing technique using pseudorabies virus. This technique has proven valuable for the identification of synaptically connected neuronal circuits. Electrical and chemical stimulation studies in anesthetized animals will identify neuronal sites which activate detrusor and sphincter activity. Chemical lesion and inactivation studies will determine the role of these neurons on bladder and urethral activity evoked by infusion of fluid into the bladder. Stimulation of the lateral tegmental field after CNS lesions will determine the contribution of rostral inputs to lateral tegmental field induced changes in bladder and urethral reflexes and pelvic, hypogastric and pudendal nerve activity. Examining the effects of CNS stimulation and inactivation at various stages of the estrous cycle, delivery after and in the retired breeder will elucidate any effects sex hormones have on bladder and urethral function in a natural setting. New information concerning the anatomical and functional specificity and/or heterogeneity of pathways mediating bladder and urethral function will be gained.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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