Spectrally distinct channelrhodopsins for two-colour optogenetic peripheral nerve stimulation.

Technologies for peripheral nerve stimulation have conventionally relied on the anatomic placement of electrodes adjacent to subsets of sensory fibres or motor fibres that selectively target an end effector. Here, we demonstrate the use of optogenetics to directly target the innervating fibres of an end effector by relying on retrograde transfection of adeno-associated virus serotype 6 to restrict axonal opsin expression to the desired fibre targets. By using an in vivo screen in rats, we identify the first channelrhodopsins as well as a halorhodopsin that respond to red light in the peripheral nerve.

Closed-loop functional optogenetic stimulation.

Optogenetics has been used to orchestrate temporal- and tissue-specific control of neural tissues and offers a wealth of unique advantages for neuromuscular control. Here, we establish a closed-loop functional optogenetic stimulation (CL-FOS) system to control ankle joint position in murine models. Using the measurement of either joint angle or fascicle length as a feedback signal, we compare the controllability of CL-FOS to closed-loop functional electrical stimulation (CL-FES) and demonstrate significantly greater accuracy, lower rise times and lower overshoot percentages.

Optogenetic Peripheral Nerve Immunogenicity.

Optogenetic technologies have been the subject of great excitement within the scientific community for their ability to demystify complex neurophysiological pathways in the central (CNS) and peripheral nervous systems (PNS). The excitement surrounding optogenetics has also extended to the clinic with a trial for ChR2 in the treatment of retinitis pigmentosa currently underway and additional trials anticipated for the near future. In this work, we identify the cause of loss-of-expression in response to transdermal illumination of an optogenetically active peroneal nerve following an anterior compartment (AC) injection of AAV6-hSyn-ChR2(H134R) with and without a fluorescent reporter.

Transdermal optogenetic peripheral nerve stimulation.

Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks.

Approach: Here we report an alternative approach involving transdermal illumination.