Abstract
Current neural interface technologies have serious limitations for advanced prosthetic and therapeutic applications due primarily to their lack of specificity in neural communication. An optogenetic approach has the potential to provide single cell/axon resolution in a minimally invasive manner by optical interrogation of light-sensitive reporters and actuators. Given the aim of reading neural activity in the peripheral nervous system, this work has investigated an activity-dependent signaling mechanism in the peripheral nerve. We demonstrate action potential evoked calcium signals in mammalian tibial nerve axons using an in vitro mouse model with a dextran-conjugated fluorescent calcium indicator. Spatial and temporal dynamics of the signal are presented, including characterization of frequency-modulated amplitude. Pharmacological experiments implicate T-type CaV channels and sodium-calcium exchanger (NCX) as predominant mechanisms of calcium influx. This work shows the potential of using calcium-associated optical signals for neural activity read-out in peripheral nerve axons.
Highlights
Current neural interface technologies have serious limitations for advanced prosthetic and therapeutic applications due primarily to their lack of specificity in neural communication
Using an in vitro rodent nerve model with axon-loaded synthetic calcium indicator, we demonstrated and characterized action potential-elicited calcium signaling in the mammalian peripheral axon
This calcium signaling was localized to the node of Ranvier, a channel-dense and metabolically active region that facilitates saltatory conduction
Summary
Current neural interface technologies have serious limitations for advanced prosthetic and therapeutic applications due primarily to their lack of specificity in neural communication. The activity-dependent calcium signaling characterized here facilitates an optogenetic approach to meet this challenge by enabling minimally invasive optical communication with specific (individual) nerve fibers. Sophisticated prostheses such as artificial hands[1, 2] have the mechanical capability to largely substitute functionality in many biological systems. The largest barrier preventing true limb replacement is the lack of an adequate neural interface that enables full and intuitive control of prosthetic devices Without this communication to the nervous system, artificial limbs and their control remain limited, capable of only crude movements and lacking sensory feedback. In contrast to electrode-based techniques of neural recording/stimulation, which cannot decipher signals from single neural pathways (rather they provide crude aggregate information from many units), optical interrogation can query many single neurons or neuron processes because the spatial resolution www.nature.com/scientificreports/
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