Journal article
Dual Effects of 5-HT1a Receptor Activation on Breathing in Neonatal Mice
The Journal of neuroscience, Vol.34(1), pp.51-59
01/01/2014
DOI: 10.1523/JNEUROSCI.0864-13.2014
PMCID: PMC3866493
PMID: 24381267
Abstract
Inhibitory 5-HT
1a
receptors are located on serotonin (5-HT) neurons (autoreceptors) as well as neurons of the respiratory network (heteroreceptors). Thus, effects on breathing of 5-HT
1a
agonists, such as (
R
)-(+)-8-hydroxy-2-(di
-N-
propylamino) tetralin (8-OH-DPAT), could either be due to decreased firing of 5-HT neurons or direct effects on the respiratory network. Mice in which the transcription factor LMX1B is genetically deleted selectively in
Pet1
-1-expressing cells (
Lmx1b
f/f/p
) essentially have complete absence of central 5-HT neurons, providing a unique opportunity to separate the effect of activation of downstream 5-HT
1a
heteroreceptors from that of autoreceptors. We used rhythmically active medullary slices from wild-type (WT) and
Lmx1b
f/f/p
neonatal mice to differentiate autoreceptor versus heteroreceptor effects of 8-OH-DPAT on hypoglossal nerve respiratory output. 8-OH-DPAT transiently increased respiratory burst frequency in
Lmx1b
f/f/p
preparations, but not in WT slices. This excitation was abolished when synaptic inhibition was blocked by GABAergic/glycinergic receptor antagonists. Conversely, after 10 min of application, frequency in
Lmx1b
f/f/p
slices was not different from baseline, whereas it was significantly depressed in WT slices. In WT mice
in vivo
, subcutaneous injection of 8-OH-DPAT produced similar biphasic respiratory effects as in
Lmx1b
f/f/p
mice. We conclude that 5-HT
1a
receptor agonists have two competing effects: rapid stimulation of breathing due to excitation of the respiratory network, and delayed inhibition of breathing due to autoreceptor inhibition of 5-HT neurons. The former effect is presumably due to inhibition of inhibitory interneurons embedded in the respiratory network.
Details
- Title: Subtitle
- Dual Effects of 5-HT1a Receptor Activation on Breathing in Neonatal Mice
- Creators
- Andrea E Corcoran - Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, Alaska 99775Kathryn G Commons - Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115Yuanming Wu - Departments of Neurology, and Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242Jeffrey C Smith - Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892Michael B Harris - Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, Alaska 99775George B Richerson - Departments of Neurology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.34(1), pp.51-59
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.0864-13.2014
- PMID
- 24381267
- PMCID
- PMC3866493
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 01/01/2014
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020603302771
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