"Characterization of a Sacral Dorsal Column Pathway Controlling Hindlimb Motor Behavior" - JoAnna T. Anderson, PhD Defense
Advisor(s): Shawn Hochman, PhD and Stephen P. DeWeerth, PhD
Committee Members: Robert Butera, PhD, T. Richard Nichols, PhD and Peter Wenner, PhD
Spinal cord injuries (SCI) sever communication between supraspinal centers and the central pattern generator (CPG) responsible for locomotion. Because the CPG is intact and retains the ability to initiate locomotor activity, it is possible to electrically and pharmacologically access the CPG pathways. The goal of this thesis was to identify a novel spinal cord surface site for electrically evoking rhythmic behavior and characterize the afferent fibers required for activating this behavior, the pathways mediating the behavior, and the resultant efferent output behaviors. Electrical activation of the locomotor CPG is a pivotal step in the development of minimally invasive neural prostheses for SCI patients. Activation of afferent pathways, specifically the dorsal column pathway, provides the unique ability to access motor systems by utilizing preexisting, natural feedback pathways; electrical stimulation of afferent fibers has been shown to evoke a locomotor-like pattern in the mammalian spinal cord.
For this research, I have selected the sacral dorsal column (sDC) as a potential surface stimulation site for evoking locomotor-like activity in the neonatal rat spinal cord. The dorsal column is an afferent fiber pathway positioned along the midline of the spinal cord’s dorsal surface. Tonic stimulation of the sDC robustly activated rhythmic left-right alternation in flexor-related ventral roots. These rhythms were dependent on the activation of TRPV1 receptor containing, high-threshold C fiber afferents. The C fibers synapsed onto spinal neurons, which project to the lumbar segments as part of a pathway dependent on purinergic, adrenergic, and cholinergic receptor activation. In ventral roots containing only somatic efferents, rhythmic activity was rarely recruited. However, in ventral roots containing both autonomic and somatic efferents, sacral dorsal column stimulation recruits autonomic efferent rhythms, which subsequently recruits somatic efferent motor rhythms. The efferent rhythms revealed a half-center organization with very low stimulation frequencies, and the evoked alternating bursts entrained to the stimuli. Similar entrainment was seen when sDC stimuli were applied during ongoing neurochemically-induced locomotor rhythms. The rhythmic patterns evoked by sDC stimulation operated over a limited frequency range, with a discrete burst structure of fast-onset, frequency-independent peaks. In comparison, neurochemically-induced locomotor bursts operated over a wide frequency range and had slower time to peaks that varied with burst frequency.
The overall findings support the discovery of an autonomic efferent pattern generator that is recruited by sacral visceral C fiber afferents. It is hoped that this research will advance the understanding of afferent activation of the lumbar central pattern generator and potentially provide insight useful for future development and design of neuroprosthetic devices.