Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice
- University of Virginia, United States
- Howard Hughes Medical Institute, Stanford University, United States
- The College of William and Mary, United States
- Washington University School of Medicine, United States
- Howard Hughes Medical Institute, Baylor College of Medicine, United States
Abstract
All motor behaviors require precise temporal coordination of different muscle groups. Breathing, for example, involves the sequential activation of numerous muscles hypothesized to be driven by a primary respiratory oscillator, the preBötzinger Complex, and at least one other as-yet unidentified rhythmogenic population. We tested the roles of Atoh1-, Phox2b-, and Dbx1-derived neurons (three groups that have known roles in respiration) in the generation and coordination of respiratory output. We found that Dbx1-derived neurons are necessary for all respiratory behaviors, whereas independent but coupled respiratory rhythms persist from at least three different motor pools after eliminating or silencing Phox2b- or Atoh1-expressing hindbrain neurons. Without Atoh1 neurons, however, the motor pools become temporally disorganized and coupling between independent respiratory oscillators decreases. We propose Atoh1 neurons tune the sequential activation of independent oscillators essential for the fine control of different muscles during breathing.
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Ethics
Animal experimentation: Experiments were done in accordance with the Institute for Laboratory Animal Research Guide for the Care and Use of Laboratory Animals. All experiments were approved by the Animal Studies Committee at Washington University School of Medicine (protocol # 20110249), the Institutional Animal Care and Use Committee at the College of William and Mary, and the Center for Comparative Medicine, Baylor College of Medicine.
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© 2014, Tupal 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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Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice
eLife 3:e02265.
https://doi.org/10.7554/eLife.02265
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Funding:
Gut2Behave project was initiated from ERA-NET NEURON network (Joint Transnational Call 2019) and was financed by Academy of Finland, French National Research Agency (ANR-19-NEUR-0003-03) and the Fonds de la Recherche Scientifique (FRS-FNRS; PINT-MULTI R.8013.19, Belgium). Metabolomics analysis of the TSDS samples was supported by grant from the Finnish Foundation for Alcohol Studies.
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