Abstract
Current neural interfaces are hampered by lack of specificity and selectivity for neural interrogation. A method that might improve these interfaces is an optical peripheral nerve interface which communicates with individual axons via optogenetic reporters. To determine the feasibility of such an interface, we delivered the genetically encoded calcium indicator GCaMP6f to the mouse peripheral nerve by intramuscular injection of adenoassociated viral vector (AAV1) under the control of the CAG (chicken beta actin- cytomegalovirus hybrid promoter). Small diameter axons in the common peroneal nerve were transduced and demonstrated electrically inducible calcium transients ex vivo. Responses to single electrical stimuli were resolvable, and increasing the number of stimuli resulted in a monotonic increase in maximum fluorescence and a prolongation of calcium transient kinetics. This work demonstrates the viability of using a virally-delivered, genetically-encoded calcium indicator to read-out from peripheral nerve axons.
Highlights
A robust interface with the nervous system in the periphery is a critical component in the restoration of function through limb reanimation in persons with spinal cord injury (SCI) and stroke[1,2], control of prosthetic limbs for individuals with limb loss[3,4], and in the exploration of peripheral neural circuits[5]
Sensory feedback plays an important role in dexterous manipulation[6], object identification[7], pain[8] the exercise pressor reflex[9,10] and reduces the amount of visual attention required for manipulating objects with either prostheses or through limb reanimation
We have demonstrated expression of GCaMP6f in small diameter axons of the murine peripheral nerve and measured robust fluorescence transients in response to electrical stimulus trains in the ex vivo preparation
Summary
A robust interface with the nervous system in the periphery is a critical component in the restoration of function through limb reanimation in persons with spinal cord injury (SCI) and stroke[1,2], control of prosthetic limbs for individuals with limb loss[3,4], and in the exploration of peripheral neural circuits[5]. Surface electroneurograms must contend with low signal strength, high noise, a limitation in the fiber size that can be read from, and distortion in signal shape[15] While some of these factors can be mitigated by using penetrating, fine-wire electrodes to measure the sensory action potential, such a method is not a robust interface for long-term use in SCI patients. Nerve cuff electrodes offer some promise in stimulation ability and serve as a backbone for functional electrical stimulation[3,16] They do not provide an effective means of interrogating small fibers, as signal recording becomes dominated by large fibers. These actuators and reporters have been www.nature.com/scientificreports/
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