EXCEED THE SPACE PROVIDED, The storage and periodic release of urine is controlledfrom several levels of the central nervous system (CNS) includingthe lumbosacral spinal cord, rostral pons, hypothalamus, subcotical nuclei,and the cerebral cortex. Various evidence indicates that the excitatory parasympathetic component of the mictudtion reflex is dependent upon supraspinal pathway originatingin the rostral pons ('pontinemicturition center' - PMC) and sending descending fibers to the sacral spinal cord. The studies outlined in the present proposal are designed to provide a detail analysis, using modem neuroanatomical, neuropharmacological and neurophysisologicaltechniques, of pontine and suprapontine structures which modulate the micturitionreflex pathway.
The aims of this proposed research are: t) To determine, usingelectrical stimulation, sites withinthe cortex, hypothalamus, and areas adjacent to hypothalamus which modulate bladder rreflexes. 2) To examine the effects of L-glutamate microinjected into those sites which give positive results (either inhibitionor facilitation)with electrical stimulation. (L-glutamate witl be used here as pharmacological tool to determine whether cell bodies or axons-in-passage are being activated by the electrical stimulation - L-glutamate being active onlyat cell bodies.) 3) To study in detail the modulation by hypothalamic and cortical sites on: a) isometric rhythmic bladder contractions, b) voiding cystometrogram (CMG), c) sympathetic input to bladder via the hypogastricnerve, d) electromyogram (EMG) of the external urethral sphincter, e) reflex evoked activityto pelvic nerve stimulationand f) single and multiunit activity at the level of the PMC and pelvic nerve efferents. 4) To determine usingimmuno- histochemical techniques the possibleneurotransmitters which mediate modulation by these suprapontine sites, and to followthese studies with neuropharmacological studies to determine the effects of agonistand especially antagonist of these putative neurotransmitters mediating the modulatory effects. 5) To determine the location of neurons in pontine and suprapontine structures (especially cortical and hypothalamic sites) which express the oncogene C-los to electrical stimulationof bladder afferents. The informationgained in this studywill not onlyprovide a much more complete wiring diagram for the micturition pathway but may also suggest possible pharmacological modificationof the act of micturition. PERFORMANCE SITE ========================================Section End===========================================
