Medullary tachykinin precursor 1 neurons promote rhythmic breathing.

Autor:	Rousseau JP; Keenan Research Centre for Biomedical Sciences. St. Michael's Hospital, Unity Health Toronto, Toronto, Canada., Furdui A; Keenan Research Centre for Biomedical Sciences. St. Michael's Hospital, Unity Health Toronto, Toronto, Canada., Silveira Scarpellini CD; Keenan Research Centre for Biomedical Sciences. St. Michael's Hospital, Unity Health Toronto, Toronto, Canada., Horner RL; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada.; Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada., Montandon G; Keenan Research Centre for Biomedical Sciences. St. Michael's Hospital, Unity Health Toronto, Toronto, Canada.; Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Jul 17; Vol. 12. Date of Electronic Publication: 2023 Jul 17.
DOI:	10.7554/eLife.85575
Abstrakt:	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 impair rhythmic breathing. Although, the 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. Competing Interests: JR, AF, CS, RH, GM No competing interests declared (© 2023, Rousseau et al.)
Databáze:	MEDLINE
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