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Modulation of Spinal Shox2 Interneurons by Synaptic Input

Friday, April 24, 2020

9:00 AM-11:00 AM

BIOMED PhD Thesis Defense

Modulation of Spinal Shox2 Interneurons by Synaptic Input from Sensory Afferents and Local Locomotor Circuits

Erik Li, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Kimberly Dougherty, PhD
Associate Professor
Department of Neurobiology and Anatomy
College of Medicine
Drexel University

Catherine Von Reyn, PhD
Assistant Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Locomotion is a complex, rhythmic motor activity involving well-coordinated activation of multiple muscle groups. Locomotor central pattern generators (CPG) are neural circuits located in the thoracolumbar spinal cord which generate the basic rhythm and pattern for locomotion. These circuits integrate descending commands and afferent feedback to produce context-appropriate gait, but the basic motor pattern can be produced independent of both signals. As a result, recruitment of CPGs may have therapeutic relevance for gait improvement following pathologies affecting descending controls, such as stroke or spinal cord injury.

Locomotor CPGs have been proposed to have a two-layer structure, in which a rhythm-generating layer produces rhythmic neural bursts and directs a pattern-forming layer to coordinate and recruit appropriate motor modules. Neurons which express the transcription factor Shox2 early in development are involved in both layers and can be divided based on overlap with the V2a interneuron class. Non-V2a Shox2 neurons are implicated in rhythm generation, while V2a Shox2 neurons contribute to motor neuron recruitment. Because rhythm-generating neurons are at the root of CPG function, modulation of non-V2a Shox2 neurons should strongly affect locomotor function. We therefore sought to determine whether and how afferent feedback and interactions with other CPG neurons contributed to the regulation of Shox2 neuron activity.

Electrical stimulation of functionally-specified ankle afferents revealed that Shox2 neurons receive highly stereotyped patterns of afferent feedback, consistent with perturbations of ongoing locomotor activity in these preparations. Synaptic inputs to non-V2a Shox2 neurons were modulated rhythmically during locomotion and were reduced following hemisection, suggesting a strong commissural component. Based on this finding, computational modeling of left-right interactions revealed that inhibitory inputs from contralateral CPGs could contribute to maintenance of Shox2 rhythmicity across a wide range of descending drive strengths and produce moderate increases in maximum locomotor frequency. Together, these results provide cellular mechanisms acting presynaptically on rhythm-generating neurons that enable context-appropriate adjustments to locomotor function.

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