title: Neuromodulation of the neural circuits controlling the lower urinary tract.
abstract: The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner.
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Parag N
authors.initials: PN
authors.lastname: Gad
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA; Brain Research Institute, University of California, Los Angeles, CA 90095, USA.
authors.forename: Roland R
authors.initials: RR
authors.lastname: Roy
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA; Pavlov Institute of Physiology, St. Petersburg 199034, Russia.
authors.forename: Yury P
authors.initials: YP
authors.lastname: Gerasimenko
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA; Neuroscience Department, International School for Advanced Studies (SISSA), Bonomea 265, Trieste, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Taccola
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA; Department of Neurobiology, University of California, Los Angeles, CA 90095, USA; Department of Neurosurgery, University of California, Los Angeles, CA 90095, USA; Brain Research Institute, University of California, Los Angeles, CA 90095, USA. Electronic address: vre@ucla.edu.
authors.forename: V Reggie
authors.initials: VR
authors.lastname: Edgerton
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy; D004567:Electrodes, Implanted; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005081:Exercise Therapy; D005260:Female; D006614:Hindlimb / Q000294:innervation; D008124:Locomotion / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009434:Neural Pathways / Q000502:physiology*; D010525:Peripheral Nerves / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications* / Q000628:therapy*; D014551:Urinary Tract / Q000503:physiopathology*; D014554:Urination / Q000502:physiology
keywords: Epidural stimulation; Locomotor training; Lower urinary tract; Tibial nerve stimulation