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Optogenetically Mediated Neuromodulation Paired with Exercised Based Rehabilitation

Friday, June 28, 2019

10:00 AM-12:00 PM

BIOMED PhD Thesis Defense

Optogenetically Mediated Neuromodulation Paired with Exercised Based Rehabilitation in Adult Transected Rats Enhances Voluntary Control of Trunk Muscle Segments Below Injury Leading to Alterations in Spinal Circuitry

Kendall Ankudovich Schmidt, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Simon F. Giszter, PhD
Neurobiology and Anatomy
Drexel University College of Medicine

After a complete T9/T10 spinal cord injury (SCI) in adult rats, trunk control becomes very important for postural stability, and crucial for function if stepping of hindlimbs is enabled. We have developed a neuromodulatory technique aimed at promoting plasticity and motor learning in the trunk motor cortex after SCI, by using subthreshold optogenetic stimulation of cortex via virally delivered Channelrhodopsin (ChR2). Virally delivered enhanced yellow fluorescent protein (EYFP) is used as a control. When optogenetically mediated neuromodulation is paired with a 25 day robot assisted rehabilitation paradigm, motor mapping studies reveal a significant increase in cortical representation of trunk muscle segments nominally below the injury in the ChR2+robot rats, both with brain derived neurotrophic factor (BDNF) induced spinal stepping and without, but not in EYFP+robot rats with or without spinal stepping enabled by BDNF. Activation of caudal trunk enabled by these representational changes also causes plastic changes in spinal circuitry below the injury by influencing sensory input and motor output from the spinal cord caudal to injury.

Monosynaptic reflex testing and Frequency Dependent Depression (FDD) is used widely to test spinal excitability. To understand chronic spinal circuit-level changes mediating trunk reflexes below injury in external oblique and longissimus, we implanted a stimulating cuff around the T13 spinal nerve, and monitored trunk muscle responses through 13 paired trunk electromyogram electrodes, spaced both above and below injury, over the course of robot rehabilitation. Due to the proximity of the stimulating cuff to the spinal cord, in ipsilateral muscle segments caudal to injury, the motor response and the reflex response overlap. Artificial neural networks can be used to separate the two signals. However, we have also discovered contralateral trunk reflex responses of comparable latency, believed to be monosynaptic, which are readily analyzed. In addition, these bilateral trunk reflexes are exhibited at multiple trunk muscle segments both above and below the injury. Neuromodulation of trunk motor cortex exhibited chronic spinal excitability and FDD differences below the injury in non-stepping rats studied and above the injury in stepping rats studied. This study highlights the multisegmental innervation of trunk muscles and the potential of trunk as a rehabilitation target after SCI.

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Ken Barbee

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