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Moallemi, Adan

University of British Columbia

Among the pathways susceptible to damage following spinal cord injury (SCI) is the corticospinal tract (CST), a supraspinal projection responsible for voluntary control of the distal limbs. Previous work has shown that enhancing cortical CST activity via neuromodulation promotes plasticity and improves motor function following SCI. However, conventional stimulation modalities either lack cell-type specificity, or do not afford temporal control of neuronal firing. The technique of optogenetics addresses these shortcomings by genetically modifying a targeted subset of neurons to express light-gated ion channels, called opsins, which enable the millisecond-scale control of neuronal firing following light exposure. Few barriers currently exist which limit the ability to study the potential plasticity-inducing effects of optogenetic stimulation of CST axons within the spinal cord in animal studies. One main barrier is a lack of validated methods for implanting light-delivery devices in the cervical spinal cord. Furthermore, blue light is conventionally used to activate blue-responsive opsins, however, it does not enable adequate tissue penetration to reach CST axons in the dorsal column. In this thesis, both challenges were studied. First, a reproducible surgical protocol was developed for the implantation of light-delivery (optoelectronic) devices in the rodent cervical spinal cord. Following one week of implantation, results demonstrate that the implant remained secured and did not cause adverse effects on motor function. Second, given that longer wavelengths of light penetrate deeper into tissue, the red-shifted opsin ChRMine was used to target the CST. Following transfection via adeno-associated virus (AAV) delivery to forelimb motor cortex (MCX), multiunit electrophysiological recordings were conducted to characterize the response profile of the CST to optogenetic stimulation at the axonal (in the spinal cord) and somatic (in MCX) level. Preliminary results demonstrate that stimulation induced local activation of CST neurons in MCX and of its axons in the spinal cord. Furthermore, modest increases in antidromic activity were recorded in MCX during CST stimulation in the spinal cord. Together, this work provides a toolkit for researchers to use in future work aimed at investigating activity-dependent plasticity mechanisms following selective optogenetic stimulation of the CST at the axonal level.

Text

2025-04-22

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/90704

Biomedical Engineering

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/