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The respiratory rhythm is also modulated by the neuropeptide substance P which is released by tachykinin-1 (Tac1)- expressing neurons. However, how tachykinergic signaling modulates the pFRG region remains incompletely understood. Here we show that substance P (1 \u00b5M, 30 nL) microinjected into the ventral pFRG increased respiratory frequency, amplitude, and minute volume under baseline conditions. These excitatory effects were abolished by prior application of the NK1 receptor antagonist GR82334, confirming NK1-mediated effect. Bilateral blockade of NK1 receptors in the ventral pFRG significantly attenuated hypercapnia-induced (FiCO\n                    <jats:sub>2<\/jats:sub>\n                    = 0.07) increases in respiratory parameters, suggesting tachykinergic signaling in CO\n                    <jats:sub>2<\/jats:sub>\n                    chemoreflex responses. Immunohistochemical analysis revealed a predominant co-localization of NK1 receptors with VGlut2-expressing glutamatergic neurons in the ventral pFRG, whereas minimal co-expression was found with GABAergic neurons. To directly assess the function of tachykinin-producing neurons, we optogenetically stimulated Tac1-expressing neurons in the ventral pFRG. Light activation produced immediate increases in respiratory rate and motor output. These findings demonstrate that tachykinin signaling in the ventral pFRG enhances respiratory output. Tac1-expressing neurons may function as an integrative hub for coordinating respiratory functions under baseline and chemoreflex conditions.\n                  <\/jats:p>","DOI":"10.1007\/s00424-025-03147-8","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T03:54:55Z","timestamp":1769140495000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tachykinergic signaling mediated by NK1 receptors in the respiratory parafacial region drives respiratory output and contributes to the chemoreflex response to CO2"],"prefix":"10.1007","volume":"478","author":[{"given":"Oct\u00e1vio A. 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