Biomechanics and electrophysiology of sensory regulation during locomotion in a novel in vitro spinal cord-hindlimb preparation

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Hayes, Heather Brant
Hochman, Shawn
Chang, Young-Hui
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The purpose of this dissertation was to gain insight into spinal sensory regulation during locomotion. To this end, I developed a novel in vitro spinal cord-hindlimb preparation (SCHP) composed of the isolated in vitro neonatal rat spinal cord oriented dorsal-up with intact hindlimbs locomoting on a custom-built treadmill or instrumented force platforms. The SCHP combines the neural and pharmacological accessibility of classic in vitro spinal cord preparations with intact sensory feedback from physiological hindlimb movements. thereby expanding our ability to study spinal sensory function. I then validated the efficacy of the SCHP for studying behaviorally-relevant, sensory-modulated locomotion by showing the impact of sensory feedback on in vitro locomotion. When locomotion was activated by serotonin and N-methyl D-aspartate, the SCHP produced kinematics and muscle activation patterns similar to the intact rat. The mechanosensory environment could significantly alter SCHP kinematics and muscle activitation patterns, showing that sensory feedback regulates in vitro spinal function. I further demonstrated that sensory feedback could reinforce or initiate SCHP locomotion. Using the SCHP custom-designed force platform system, I then investigated how presynaptic inhibition dynamically regulates sensory feedback during locomotion and how hindlimb mechanics influence this regulation. I hypothesized that contralateral limb mechanics would modulate presynaptic inhibition on the ipsilateral limb. My results indicate that contralateral limb stance-phase loading regulates ipsilateral swing-phase sensory inflow. As contralateral stance-phase force increases, contralateral afferents act via a GABAergic pathway to increase ipsilateral presynaptic inhibition, thereby inhibiting sensory feedback entering the spinal cord. Such force-sensitive contralateral presynaptic inhibition may help preserve swing, coordinate the limbs during locomotion, and adjust the sensorimotor strategy for task-specific demands. This work has important implications for sensorimotor rehabilitation. After spinal cord injury, sensory feedback is one of the few remaining inputs available for accessing spinal locomotor circuitry. Therefore, understanding how sensory feedback regulates and reinforces spinally-generated locomotion is vital for designing effective rehabilitation strategies. Further, sensory regulation is degraded by many neural insults, including spinal cord injury, Parkinson's disease, and stroke, resulting in spasticity and impaired locomotor function. This work suggests that contralateral limb loading may be an important variable for restoring appropriate sensory regulation during locomotion.
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