Abstract
Novel clinical treatments to target peripheral nerves are being developed which primarily use electrical current. Recently, infrared (IR) light was shown to inhibit peripheral nerves with high spatial and temporal specificity. Here, for the first time, we demonstrate that IR can selectively and reversibly inhibit small-diameter axons at lower radiant exposures than large-diameter axons. We provide a mathematical rationale, and then demonstrate it experimentally in individual axons of identified neurons in the marine mollusk Aplysia californica, and in axons within the vagus nerve of a mammal, the musk shrew Suncus murinus. The ability to selectively, rapidly, and reversibly control small-diameter sensory fibers may have many applications, both for the analysis of physiology, and for treating diseases of the peripheral nervous system, such as chronic nausea, vomiting, pain, and hypertension. Moreover, the mathematical analysis of how IR affects the nerve could apply to other techniques for controlling peripheral nerve signaling.
Highlights
Small-diameter axons play critical roles in sensory and motor systems
Analysis of extracellular current application to peripheral nerves has demonstrated that larger-diameter axons are affected more than smaller-diameter axons, because current induced within the axon is proportional to axonal cross-section[9]
Excitation using IR light has been demonstrated for cochlear implants, cortical stimulation, cardiac pacing, and the control of peripheral nerves[11,12,13,14]
Summary
To test whether populations of small-diameter unmyelinated fibers would be selectively inhibited by IR light, we used the pleural-abdominal connective of Aplysia [Figure S3 - setup], containing only unmyelinated axons whose most common axonal diameter ranges from 0.8–3 μm[30]. Electrical stimulation of the nerve generated a compound action potential (CAP), which included fast-conducting (large-diameter) and slow-conducting (small-diameter) axons. These components separate from one another over the length of the nerve. To test whether populations of small-diameter axons in vertebrates can be preferentially inhibited, even though they have different complements of ion channels than those in Aplysia, we studied the vagus of a mammal, the musk shrew Suncus murinus, a species used for emesis research on the vagus nerve because rats and mice lack an emetic reflex[31]. In combination with other techniques, this approach could create novel methods for controlling, analyzing, and treating diseases of the nervous system
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