Neuromodulation of spinal autonomic regulation

Sympathetic preganglionic;Electrophysiology;Presynaptic inhibition;Monoamine;Visceral afferent;Sympathetic;Spinal cord

Zimmerman, Amanda L. ; Biomedical Engineering

University:Georgia Institute of Technology

Department:Biomedical Engineering

关键词: Sympathetic preganglionic;    Electrophysiology;    Presynaptic inhibition;    Monoamine;    Visceral afferent;    Sympathetic;    Spinal cord;   

Others  :  https://smartech.gatech.edu/bitstream/1853/42777/1/zimmerman_amanda_l_201112_phd.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

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 ofthe 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.