Electrophysiologic, pharmacologic and neuroanatomical techniques will be used to investigate the brain stem and spinal cord mechanisms that integrate autonomic and somatic efferent pathways controlling lower urinary tract function in the cat and rat. The LUT is ideal for studying viscerosomatic interactions since it has only two functions (storage and release of urine) which are regulated by simple """"""""on-off"""""""" switching circuits in the central nervous system and which require a close coordination between autonomic and somatic efferent organs. This study will examine the organization of and neurotransmitter mechanisms involved in the micturition switching circuitry in the pons and lumbosacral spinal cord. Several hypotheses will be tested: (1) multiple transmitter systems (enkephalinergic, GABAergic, dopaminergic and cholinergic) contribute to the pontine control of micturition, (2) urine storage and release are regulated by separate populations of neurons in the pons, many of which send axonal projections to the lumbosacral cord where they modulate spinal interneuronal mechanisms that control the efferent outflow to the bladder and urethral sphincter, (3) in normal animals, spinal reflex pathways play an important role in urine storage, but a relatively minor role in urine release, which is controlled by spinobulbospinal pathways. However, following spinal cord damage or local disorders in the urinary tract such as partial urethral obstruction, spinal reflex mechanisms can assume a major role in the initiation of micturition, (4) emergence or facilitation of spinal reflex mechanisms is an important factor in the development of bladder hyperreflexia and uncoordinated bladder-sphincter activity, (5) the micturition reflex pathway exhibits considerable plasticity both in young animals during postnatal development as well as in adult animals in response to neural injury or peripheral pathology. A part of this plasticity is attributable to changes in primary afferent input to the spinal cord, which then leads to changes in the properties of central synapses. The ultimate objective in this investigation is to provide a wiring diagram for the central pathways which coordinate the autonomic and somatic efferent outflow to the LUT. Considerable data is available about the characteristics of incoming and outgoing signals from the spinal cord, but and efferent pathways in the autonomic system or which mediate somatic modulation of autonomic function. The identification of neurotransmitters in these pathways and the elucidation of the mechanisms contributing to the reorganization of visceral reflexes following spinal cord injury or urethral obstruction may lead to new therapeutic approaches for the management of prostatic disease as well as neurogenic disorders of the lower urinary tract.
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