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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Autonomic Neuroscience
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1386737
This article is part of the Research Topic Cardio-Respiratory-Brain Integrative Physiology: Interactions, Mechanisms, and Methods for Assessment View all articles

Postinspiratory and preBötzinger complexes contribute to respiratorysympathetic coupling in mice before and after chronic intermittent hypoxia

Provisionally accepted
Marlusa Karlen-Amarante Marlusa Karlen-Amarante 1Zachary T. Glovak Zachary T. Glovak 1Alyssa Huff Alyssa Huff 1Luiz M. Oliveira Luiz M. Oliveira 1Jan-Marino Ramirez Jan-Marino Ramirez 1,2*
  • 1 Seattle Children's Research Institute, Seattle, Washington, United States
  • 2 University of Washington, Seattle, Washington, United States

The final, formatted version of the article will be published soon.

    The sympathetic nervous system modulates arterial blood pressure. Individuals with obstructive sleep apnea (OSA) experience numerous nightly hypoxic episodes and exhibit elevated sympathetic activity to the cardiovascular system leading to hypertension. This suggests that OSA disrupts normal respiratory-sympathetic coupling. This study investigates the role of the postinspiratory complex (PiCo) and preBötzinger complex (preBötC) in respiratory-sympathetic coupling under control conditions and following exposure to chronic intermittent hypoxia (CIH) for 21 days (5% O2 – 80 bouts/day). The surface of the ventral brainstem was exposed in urethane (1.5 g/kg) anesthetized, spontaneously breathing adult mice. Cholinergic (ChAT), glutamatergic (Vglut2), and neurons that co-express ChAT and Vglut2 at PiCo, as well as Dbx1 and Vglut2 neurons at preBötC, were optogenetically stimulated while recording activity from the diaphragm (DIA), vagus nerve (cVN), and cervical sympathetic nerve (cSN). Following CIH exposure, baseline cSN activity increased, breathing frequency increased, and expiratory time decreased. In control mice, stimulating PiCo specific cholinergic-glutamatergic neurons caused a sympathetic burst during all phases of the respiratory cycle, whereas optogenetic activation of cholinergic-glutamatergic PiCo neurons in CIH mice increased sympathetic activity only during postinspiration and late expiration.. Stimulation of glutamatergic PiCo neurons increased cSN activity during the postinspiratory phase in control and CIH mice. Optogenetic stimulation of ChAT containing neurons in the PiCo area did not affect sympathetic activity under control or CIH conditions. Stimulating Dbx1 or Vglut2 neurons in preBötC evoked an inspiration and a concomitant cSN burst under control and CIH conditions. Taken together, these results suggest that PiCo and preBötC contribute to respiratory-sympathetic coupling, which is altered by CIH, and may contribute to the hypertension observed in patients with OSA.

    Keywords: chronic intermittent hypoxia, sympathetic activity, post-inspiratory complex, PreBötzinger Complex, Optogenetics (key words)

    Received: 16 Feb 2024; Accepted: 16 Apr 2024.

    Copyright: © 2024 Karlen-Amarante, Glovak, Huff, Oliveira and Ramirez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jan-Marino Ramirez, Seattle Children's Research Institute, Seattle, 98101, Washington, United States

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