In spite of great progress in recent years, in the understanding of the neural control of sexual behavior, there is still a large gap in our understanding of how forebrain control is exerted on the spinal systems mediating sexual reflexes. A major issue to be addressed in this proposal is the brainstem pathways and mechanisms that mediate activation of sexual reflexes by the medial preoptic area of the hypothalamus. The Principal Investigator has recently developed a novel experimental approach in which behaviorally meaningful genital reflexes, specifically erectile and ejaculatory responses, can be elicited in anesthetized rats. This model provides a unique means of studying integrated central nervous system control of sexual function. The foundation of these experiments is a method in which the urethral bulb is either mechanically stimulated or infused with saline during constriction of the urethral meatus. Such stimulation elicits what the Principal Investigator calls the urogenital reflex, which consists of penile erection, ejaculation, and clonic contractions of the striated perineal muscles. The reflex lasts for an average of about eighteen seconds and can be produced in urethane-anesthetized, spinalized rats. Recent studies have demonstrated that this reflex is normally tonically inhibited by descending influences from the paragigan to cellular nucleus in the ventromedial medulla. This descending influence apparently utilizes serotonin as a principal neurotransmitter. Destruction of this descending system disinhibits ejaculatory reflexes in copulating rats and neurotoxic destruction of descending serotonin systems disinhibit the reflex in spinalized animals as well. In this proposal, the urethrogenital reflex would be used to identify the brain stem sites that relay activation of genital reflexes in response to stimulation of the medial preoptic region. A coordinated series of an anatomical and physiological experiments would be performed to identify the pathways by which the medial preoptic region exerts control over the lumbosacral spinal cord. Brain stem sites projecting to spinal nuclei controlling male genital reflexes would be identified by the transneuronal tracing technique using pseudorabies virus. This technique has proven valuable for the identification of synaptically connected neuronal circuits. Additional electrical and chemical stimulation studies in anesthetized animals will identify neuronal sites in the preoptic region that activate sexual reflexes. In separate anatomical studies, these active regions will be injected with more conventional anterograde and retrograde tracers fluorogold and neurobiotin as an independent verification of pathways labeled with the pseudorabies method. The pathways involved in sexual reflex function will be thus identified by coordinated electrical and chemical stimulation studies. Combination of the anatomical and physiological techniques is expected to identify locations of neurons and fibers that are functionally related to the control of sexual function in this model system. Preliminary studies have identified the periaqueductal gray of the midbrain as a region activating sexual reflexes in a manner similar to the medial preoptic region. This observation suggests that the periaqueductal gray is a relay for descending activation from the medial preopticregion, a hypothesis that will be tested by a combination of tract tracing and stimulation studies.
| Gonzalez, C M; Brannigan, R E; Bervig, T et al. (2001) Protein and gene expression of nitric oxide synthase isoforms I and III in the rat penile shaft. J Androl 22:54-61 |
| McKenna, K E (2001) Neural circuitry involved in sexual function. J Spinal Cord Med 24:148-54 |
| Gonzalez, C M; Bervig, T; Podlasek, C et al. (1999) Sildenafil causes a dose- and time-dependent downregulation of phosphodiesterase type 6 expression in the rat retina. Int J Impot Res 11 Suppl 1:S9-14 |
| McKenna, K E (1998) Central control of penile erection. Int J Impot Res 10 Suppl 1:S25-34 |
| McVary, K T; Rathnau, C H; McKenna, K E (1997) Sexual dysfunction in the diabetic BB/WOR rat: a role of central neuropathy. Am J Physiol 272:R259-67 |
| Marson, L; McKenna, K E (1996) CNS cell groups involved in the control of the ischiocavernosus and bulbospongiosus muscles: a transneuronal tracing study using pseudorabies virus. J Comp Neurol 374:161-79 |
