Nathan Kirkpatrick defended his PhD on January 15, 2025. Congratulations Nathan! Nathan will soon be starting a job as a Senior Research and Development Engineer at Boston Scientific in Minneapolis.
Committee Members:
Robert Butera, PhD (Co-Advisor); Young-Hui Chang, PhD (Co-Advisor); Gordon Berman, PhD; Timothy Cope, PhD; Omer Inan, PhD; Anqi Wu, PhD
Title: Novel methods to study adaptation to nerve injury
Abstract
Animals need to be able to rapidly overcome neuromuscular injury and maintain locomotion to survive. Traditional nerve transection techniques have shown that adaptation priorities emerge over days to weeks, ultimately re-establishing overall limb length despite joint-level deficits. However, these methods offer limited insights into the initial seconds to minutes following nerve or muscle dysfunction. Analysis of accurate kinematics data is time and resource intensive, and the post-operative recovery period effects early-stage gait. To address this gap, we paired machine learning-based kinematics processing and analysis tools with a quickly reversible, on-demand nerve conduction block. We hypothesized that rats would begin to adapt immediately with temporary nerve injury and also exhibit signs of compensatory adjustments with repeated exposure as indicated by a burgeoning prioritization of the overall limb length over time. Furthermore, we hypothesized that the earliest period of adaptation to nerve injury would involve feedforward control strategies to maintain overall limb length such that an after-effect would be present when nerve signaling returned. To test this, we inhibited muscle nerve signaling in rats performing treadmill locomotion during 4 separate sessions. In support of our hypotheses, limb length began to be conserved immediately during nerve block, and we observed additional changes by session 4. After-effects were also seen; during post-block, limb length initially over-corrected before returning to baseline. This un-paralleled glimpse into rapid adaptation to nerve injury support a compensatory timescale much shorter than previously thought and expand our understanding of neuroplasticity as it relates to the control of legged locomotion.