# Tachykinergic signaling mediated by NK1 receptors in the respiratory parafacial region drives respiratory output and contributes to the chemoreflex response to CO2

## TL;DR

This study shows that tachykinergic signaling in the pFRG region boosts breathing and helps the body respond to CO2 changes.

## Contribution

The study reveals a novel role of NK1 receptors in modulating respiratory output and CO2 chemoreflex via tachykinin signaling in the pFRG.

## Key findings

- Substance P microinjection into the pFRG increases respiratory parameters, which are blocked by NK1 antagonists.
- Blocking NK1 receptors in the pFRG reduces the respiratory response to CO2.
- Optogenetic stimulation of Tac1 neurons in the pFRG increases respiratory rate and motor output.

## Abstract

The respiratory parafacial region (pFRG) contributes critically to central chemoreception, CO2/H+ homeostasis and the regulation of all major components of the respiratory rhythm. 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 µM, 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 (FiCO2= 0.07) increases in respiratory parameters, suggesting tachykinergic signaling in CO2 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.