Biophysical modeling to reverse engineer two mammalian neural circuits lower urinar Y tract and hippocampus

Computational neuroscience provides tools to abstract and generalize principles of neuronal function using mathematics and computers. This dissertation reports biophysical modeling approaches to facilitate reverse engineering of two mammalian neural circuits - the lower urinary tract for the development of stimulation techniques, and the rodent hippocampus to understand mechanisms involved in theta rhythms. The LUT in mammals consists of the urinary bladder, external urethral sphincter (EUS) and the urethra. Control of the LUT is achieved via a neural circuit which integrates distinct components. Dysfunctions of the lower urinary tract (LUT) are caused by a variety of factors including spinal cord injury and diabetes. Our model builds on previous models by using biologically realistic spiking neurons to reproduce neural control of the LUT in both normal function and dysfunction cases. The hippocampus has long been implicated in memory storage and retrieval. Also, hippocampal theta oscillations (4-12 Hz) are consistently recorded during memory tasks and spatial navigation. Previous model revealed five distinct theta generators. The present study extends the work by probing deeper into the intrinsic theta mechanisms via characterizing the mechanisms as being resonant, i.e., inherently produce theta, or synchronizing, i.e., promote coordinated activity, or possibly both. The role of the neuromodulatory state is also investigated.Includes bibliographical references (pages 157-164)

Respuesta de la musculatura del piso pélvico a la estimulación eléctrica transcutánea del nervio pudendo durante la biorretroalimentación para incontinencia urinaria de urgencia

ANTECEDENTES: La incontinencia urinaria de urgencia es una alteración con elevada prevalencia en México (60%), asociada con diversos grados de incapacidad para la vida diaria. El tratamiento incluye terapia conductual y neuromodulación.OBJETIVO: Evaluar la reacción de la musculatura del piso pélvico durante la biorretroalimentación asistida por estimulación eléctrica transcutánea del nervio pudendo en pacientes con incontinencia urinaria de urgencia.MATERIALES Y MÉTODOS: Estudio observacional, longitudinal, no experimental, llevado a cabo en pacientes con incontinencia urinaria de urgencia, quienes recibieron tratamiento conductual con biorretroalimentación asistida por estimulación eléctrica transcutánea del nervio pudendo. Se registraron las variables de edad, evolución y parámetros del diario vesical. Se utilizó un equipo de urodinamia (Andromeda®) con transductor transrectal, se registró la perineometría en reposo, en contracción voluntaria de la musculatura del piso pélvico y durante la electroestimulación transcutánea del nervio pudendo con estimulación neuromuscular EMS+2 (Staodyn®). Para el análisis de los datos se utilizó el programa SPSS 10.1 (IC95% y prueba t de Student).RESULTADOS: Se registraron 14 pacientes, con media de edad de 59.8 ± 11.80 años. Durante la primera sesión la media de perineometría en reposo fue 1.21 ± 0.42 cmH20, en contracción voluntaria 13.64 ± 7.09 cmH20 y con electroestimulación transcutánea del nervio pudendo 46.4 ± 7.14 cmH20 (p<0.05). No se reportaron reacciones adversas.CONCLUSIONES: La intensa contracción de la musculatura del piso pélvico (50 cmH2O), provocada por la estimulación eléctrica transcutánea del nervio pudendo durante la biorretroalimentación representa una técnica de neuromodulación efectiva, fácil de utilizar y con alta reproducibilidad en pacientes con incontinencia urinaria de urgencia.PALABRAS CLAVE: Incontinencia urinaria de urgencia; biorretroalimentación; neuromodulación; nervio pudendo; electroestimulación

Pudendal nerve stimulation induces urethral contraction and relaxation

In this study we measured urethral pressure changes in response to efferent pudendal nerve stimulation in rats. All other neural pathways to the urethra were transected, and the urethra was continuously perfused. We found fast twitch-like contractions, superimposed on a slow relaxation. The amplitude of the twitches was independent of the stimulation frequency below 26 Hz, whereas the relaxation depended highly on this frequency. The twitches were caused by striated urethral muscles, and the relaxation was caused by smooth muscles. Both were mediated by acetylcholine. We calculated the effective urethral relaxation as the absolute relaxation multiplied by the time fraction between the twitches. Maximum effective relaxation occurred at 8-10 Hz, exactly the frequency of spontaneous oscillations during bladder voiding in rats. Although the oscillatory sphincter contractions in rats during voiding may be needed in other mechanisms for efficient voiding, our data suggest that they may be a side effect of the actual purpose: urethral relaxation