Rhythmic breathing is generated by neural circuits located in the brainstem. At its core is the preBötzinger Complex (preBötC), a region of the medulla, necessary for the generation of rhythmic breathing in mammals. The preBötC is comprised of various neuronal populations expressing neurokinin-1 receptors, the cognate G-protein-coupled receptor of the neuropeptide substance P (encoded by the tachykinin precursor 1 or Tac1). Neurokinin-1 receptors are highly expressed in the preBötC and destruction or deletion of neurokinin-1 receptor-expressing preBötC neurons severely impairs rhythmic breathing. Although application of substance P to the preBötC stimulates breathing in rodents, substance P is also involved in nociception and locomotion in various brain regions, suggesting that Tac1 neurons found in the preBötC may have diverse functional roles. Here, we characterized the role of Tac1-expressing preBötC neurons in the generation of rhythmic breathing in vivo, as well as motor behaviors. Using a cre‑lox recombination approach, we injected adeno-associated virus containing the excitatory channelrhodopsin-2 ChETA in the preBötC region of Tac1-cre mice. Employing a combination of histological, optogenetics, respiratory, and behavioral assays, we showed that stimulation of glutamatergic or Tac1 preBötC neurons promoted rhythmic breathing in both anesthetized and freely moving animals, but also triggered locomotion and overcame respiratory depression by opioid drugs. Overall, our study identified a population of excitatory preBötC with major roles in rhythmic breathing and behaviors.
All data generated are included in the manuscript and supporting files.Source data files are provided for all Figures.
- Jean-Philippe Rousseau
- Gaspard Montandon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All procedures were carried out in accordance with the recommendations of the Canadian Council on Animal Care and were approved by St. Michael's Hospital animal care committee (animal use protocols #981 and #988).
- Jeffrey C Smith, National Institute of Neurological Disorders and Stroke, United States
© 2023, Rousseau et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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