Journal article
Medullary 5-HT neurons: Switch from tonic respiratory drive to chemoreception during postnatal development
Neuroscience, Vol.344, pp.1-14
03/06/2017
DOI: 10.1016/j.neuroscience.2016.09.002
PMCID: PMC5303637
PMID: 27619736
Abstract
•Early postnatal ages 5-HT neurons provide tonic drive to the respiratory network only.•Early postnatal ages 5-HT neurons do not contribute to chemoreception.•5-HT neurons from P21 animals switch their role from tonic drive to chemoreceptors.•Our results could be related to the ventilatory abnormalities proposed in SIDS.
Serotonin (5-HT) neurons contribute to respiratory chemoreception in adult mice, but it is unclear whether they play a similar role in neonatal mice. We studied breathing during development in Lmx1bf/f/p mice, which lack 5-HT neurons. From postnatal days 1–7 (P1–P7), ventilation of Lmx1bf/f/p mice breathing room air was 50% of WT mice (p<0.001). By P12, baseline ventilation increased to a level equal to WT mice. In contrast, the hypercapnic ventilatory response (HCVR) of neonatal Lmx1bf/f/p and WT mice was equal to each other, but were both much less than adult WT mice. By P21 the HCVR of WT mice increased to near adult levels, but the HCVR of Lmx1bf/f/p mice had not changed, and was 42% less than WT mice. Primary cell cultures were prepared from the ventromedial medulla of neonatal mice, and patch-clamp recordings were made from neurons identified as serotonergic by expression of a reporter gene. In parallel with developmental changes of the HCVR in vivo, 5-HT neurons had little chemosensitivity to acidosis until 12days in vitro (DIV), after which their response increased to reach a plateau around 25 DIV. Neonatal Lmx1bf/f/p mice displayed high mortality and decreased growth rate, and this worsened in hypoxia. Mortality was decreased in hyperoxia. These results indicate that maturation of 5-HT neurons contributes to development of respiratory CO2/pH chemoreception during the first few weeks of life in mice in vivo. A defect in the 5-HT system in early postnatal life decreases survival due in part to hypoxia.
Details
- Title: Subtitle
- Medullary 5-HT neurons: Switch from tonic respiratory drive to chemoreception during postnatal development
- Creators
- Veronica J Cerpa - Department of Neurology, Yale University, New Haven, CT 06510, United StatesYuanming Wu - Department of Neurology, Yale University, New Haven, CT 06510, United StatesEduardo Bravo - Department of Neurology, University of Iowa, Iowa City, IA 52242, United StatesFrida A Teran - Department of Neurology, University of Iowa, Iowa City, IA 52242, United StatesRachel S Flynn - Department of Neurology, Yale University, New Haven, CT 06510, United StatesGeorge B Richerson - Department of Neurology, Yale University, New Haven, CT 06510, United States
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.344, pp.1-14
- DOI
- 10.1016/j.neuroscience.2016.09.002
- PMID
- 27619736
- PMCID
- PMC5303637
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: P20NS076916, P01HD36379, R01HD052772, U01NS090414
- Language
- English
- Date published
- 03/06/2017
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020746102771
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