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OPTICAL CONTROL OF PERIPHERAL NERVE SIGNAL TRANSMISSION
Presenter: Sahil K Kapur, MD
Co-Authors: Richner T; Williams JC; Poore SO
UNIVERSITY OF WISCONSIN MADISON

Objective: Precise control over signals transmitted via peripheral nerves can promote significant advances in the management of acute and chronic pain, muscle spasticity and the integration of neural prostheses. Current technology, involving electrical stimulation significantly damages the nerves being manipulated. Optogenetic technology enables us to optically control peripheral nerve signals without leading to nerve injury. Our goal is to demonstrate optical augmentation and inhibition of neural signals in transgenic mice expressing light sensitive ion channels.

Methods: Optogenetically modified transgenic mice were anesthetized and the sciatic nerve and its target muscles were surgically exposed in accordance with university IACUC guidelines. A software based control algorithm was implemented to detect a signal travelling distally along the sciatic nerve and transmit a synchronized optical pulse to the target muscle. Proximally travelling signals were detected and intercepted with a synchronized optical pulse directed at the sciatic nerve.

Results: Analysis of electromyographic and electroneurographic signals recorded in 980 trials in 10 transgenic mice demonstrate the use of synchronized optical pulses to achieve precise graded augmentation and inhibition of signals travelling proximally and distally along the sciatic nerve. This phenomenon was not detected in control experiments. Expression of transgenes that allow optical control are demonstrated in histologic preparations.

Conclusion: The ability to augment or inhibit a peripheral nerve signal and its response in a target muscle has potential benefits in augmentation of activity in paretic muscles, reduction of activity in hyperactive muscles and synchronization of activity with integrated prostheses. Furthermore, the ability to reversibly and precisely block a signal travelling towards the central nervous system from the periphery has profound implications in the area of acute and chronic pain management.


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