The central nervous system is largely responsible for receiving sensory information from the environment and determining motor output. Yet, centrally-derived behavior and sensation depends on the optimal maintenance of the cells, tissues, and organs that feed and support these functions. Most of visceral regulation occurs without conscious oversight, making the spinal cord a key site for integration and control. How the spinal cord modulates output to our organs, or sensory information from them, is poorly understood. The overall aim of this dissertation was to better understand spinal processing of both visceral sensory information to and sympathetic output from the spinal cord. I first established and validated a HB9-GFP transgenic mouse model that unambiguously identified sympathetic preganglionic neurons (SPNs), the spinal output neurons for the sympathetic nervous system. Using this model, I investigated the electrophysiological similarities and diversity of SPNs, and compared their active and passive membrane properties to those in other animal models. My results indicate that while many of the same characteristics are shared, SPNs are a heterogeneous group that can be differentiated based on their electrophysiological properties. Since descending monoaminergic pathways have particularly dense projections to sympathetic regions of the spinal cord, I next examined the modulatory role that the monoamines have on spinal sympathetic output. While each neuromodulator tested had a unique signature of action, serotonin and norepinephrine appeared to increase the excitability of individual SPNs, while dopamine had more mixed actions. Since many autonomic reflexes are integrated by the spinal cord, I also questioned whether these reflexes would be similarly modulated. I therefore developed a novel in vitro spinal cord and sympathetic chain preparation, which allowed for the investigation of visceral afferent-mediated reflexes and their neuromodulation by monoamines. This preparation exposed a dichotomy of action, where sympathetic and somatic motor output is generally enhanced by the monoamines, but reflexes mediated by visceral input are depressed. Utilizing the spinal cord and sympathetic chain preparation, I also investigated how the spinal cord modulates visceral sensory information. One of the most powerful means of selectively inhibiting afferent information from reaching the spinal cord is presynaptic inhibition. I hypothesized that both spinal visceral afferents and descending monoaminergic systems would depress transmission of visceral afferents to the spinal cord. My results demonstrated that activity in spinal visceral afferents can lead to spinally generated presynaptic inhibition, and that in addition to depressing synaptic transmission to the spinal cord, the monoamines also depress the intrinsic circuitry that generates this activity-dependent presynaptic inhibition. Taken together, my results indicate that descending monoaminergic pathways act to limit the amount of visceral sensory information reaching the central nervous system and increase sympathetic output, resulting in an uncoupling of output from visceral sensory input and transitioning to a feed-forward, sympathetically dominant control strategy. This combination offers complex modulatory strategies for descending systems.

Despite years of research, females continue to have a higher incidence of non-contact ACL injuries. One of the major findings of this research is that males and females perform certain tasks, such as, cutting, landing, and single-leg squatting, differently. In particular, females tend to move the knee into a more valgus position; a motion putting the ACL at risk for injury. Yet the underlying spinal control mechanisms modulating this motion are unknown. Additionally, the mechanisms regulating the ability to rapidly initiate and produce maximal torque are also unknown. Therefore, the purpose was to: 1) determine if the sexes modulate spinal control differently, 2) examine the contributions of spinal control mechanisms to valgus knee motion, and 3) identify contributions of spinal control to the ability to rapidly produce force. The spinal control variables were the first derivative of the Hoffmann (H)-reflex, the first derivative of extrinsic pre-synaptic inhibition (EPI), the first derivative of intrinsic pre-synaptic inhibition (IPI), recurrent inhibition (RI), and V-waves. To assess the neuromuscular system’s ability to rapidly activate, rate of torque development (RTD) and electromechanical delay (EMD) were measured. Lastly, valgus motion was determined by the frontal plane projection angle (FPPA). The results reveal males and females do modulate spinal control differently; specifically males had an increased RTD, which is the slope of the torque-time curve, and increased RI, which is a post-synaptic regulator of torque output. However, the spinal control mechanisms did not significantly contribute to FPPA at the knee. EMD which is the time lag from muscle activity to torque production was significantly predicted by the spinal control mechanisms. Specifically, EPI, a modulator of afferent inflow from peripheral and descending sources, IPI, a regulator of Ia afferent inflow, and sex significantly contributed to EMD. Lastly, the spinal control mechanisms significantly contributed to RTD. Specifically, IPI, sex, and V-waves, a measure of supraspinal drive, all significantly contributed to RTD. / Graduation date: 2009