Why the study?
Selective bioelectronic activation of small, unmyelinated C-afferents could help study and treat peripheral organ diseases involving vagal reflexes, but had not been achieved.
Does kHz-frequency electrical stimulation selectively activate vagal C-afferents in rats and mice?
Does kHz-frequency electrical stimulation selectively activate vagal C-afferents in rats and mice?
kHz-frequency electrical stimulation provides a novel neuromodulation strategy to selectively activate vagal C-afferents over larger fibers, enabling targeted study of autonomic reflexes.
Answers are grounded in this paper and cite their sources.
May enable selective vagal C-afferent studies in rodents; leaves open translation to human neuromodulation.
BACKGROUND: Vagal reflexes regulate homeostasis in visceral organs and systems through afferent and efferent neurons and nerve fibers. Small, unmyelinated, C-type afferents comprise over 80% of fibers in the vagus and form the sensory arc of autonomic reflexes of the gut, lungs, heart and vessels and the immune system. Selective bioelectronic activation of C-afferents could be used to mechanistically study and treat diseases of peripheral organs in which vagal reflexes are involved, but it has not been achieved. METHODS: We stimulated the vagus in rats and mice using trains of kHz-frequency stimuli. Stimulation effects were assessed using neuronal c-Fos expression, physiological and nerve fiber responses, optogenetic and computational methods. RESULTS: Intermittent kHz stimulation for 30 min activates specific motor and, preferentially, sensory vagus neurons in the brainstem. At sufficiently high frequencies (>5 kHz) and at intensities within a specific range (7-10 times activation threshold, T, in rats; 15-25 × T in mice), C-afferents are activated, whereas larger, A- and B-fibers, are blocked. This was determined by measuring fiber-specific acute physiological responses to kHz stimulus trains, and by assessing fiber excitability around kHz stimulus trains through compound action potentials evoked by probing pulses. Aspects of selective activation of C-afferents are explained in computational models of nerve fibers by how fiber size and myelin shape the response of sodium channels to kHz-frequency stimuli. CONCLUSION: kHz stimulation is a neuromodulation strategy to robustly and selectively activate vagal C-afferents implicated in physiological homeostasis and disease, over larger vagal fibers.
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Chang et al. (2022) studied this question.
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