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kHz-frequency electrical stimulation selectively activates small, unmyelinated vagus afferents

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 an...

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Detalles Bibliográficos
Autores principales: Chang, Yao-Chuan, Ahmed, Umair, Jayaprakash, Naveen, Mughrabi, Ibrahim, Lin, Qihang, Wu, Yi-Chen, Gerber, Michael, Abbas, Adam, Daytz, Anna, Gabalski, Arielle H., Ashville, Jason, Dokos, Socrates, Rieth, Loren, Datta-Chaudhuri, Timir, Tracey, Kevin J., Guo, Tianruo, Al-Abed, Yousef, Zanos, Stavros
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164362/
https://www.ncbi.nlm.nih.gov/pubmed/36241025
http://dx.doi.org/10.1016/j.brs.2022.09.015
Descripción
Sumario: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.