Viral-mediated optogenetic techniques for peripheral nerve stimulation of motor function

/Abstract This project seeks to improve the utility of viral optogenetic nerve stimulation for the purpose of stimulating muscle activity and movements. Given the unique challenges of viral optogenetic stimulation in the peripheral nervous system and no examinations of such techniques in the pathological context of chronic motor injury to date, we will address the following related goals in this project. We will first examine and compare the responses of optogenetic nerve stimulation of muscle activity with functional electrical stimulation (FES) in a rodent model of spinal cord injury and any accompanying chronic neuromuscular changes. We will then characterize the baseline specificity of how motor vs. sensory neurons and their peripheral axons are labeled with light-sensitive opsins in targeted nerves after intramuscular virus injection using several recently developed adeno-associated virus (AAV) serotypes or other vector design strategies. These histological results will also be correlated with muscle response signatures to assess the functional effect of such labelling patterns. Finally, we will demonstrate the feasibility of these techniques for optogenetically stimulating paralyzed muscle function in awake behaving animals during locomotion via novel chronically implanted nerve interfaces capable of both optical and electrical stimulation, enabling us to directly compare optically stimulated muscle responses and movements to those elicited using comparable electrical nerve stimulation. After completion of these aims, we will have not only demonstrated the significance and high potential utility of peripheral optogenetic nerve stimulation for motor rehabilitation purposes such as in spinal cord injury, but we will have also developed innovative approaches and tools to improve viral peripheral optogenetic nerve stimulation for a broader array of peripheral nerve applications. Project Number: 1R01NS142067-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Jordan Williams | Institution: MEDICAL COLLEGE OF WISCONSIN, MILWAUKEE, WI | Award Amount: $351,840 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 NINC-Q (01)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11293965