Journal article
Raphé Neurons Stimulate Respiratory Circuit Activity by Multiple Mechanisms via Endogenously Released Serotonin and Substance P
The Journal of neuroscience, Vol.29(12), pp.3720-3737
03/25/2009
DOI: 10.1523/JNEUROSCI.5271-08.2009
PMCID: PMC2940110
PMID: 19321769
Abstract
Brainstem serotonin (5-HT) neurons modulate activity of many neural circuits in the mammalian brain, but in many cases endogenous mechanisms have not been resolved. Here, we analyzed actions of raphé 5-HT neurons on respiratory network activity including at the level of the pre-Bötzinger complex (pre-BötC) in neonatal rat medullary slices
in vitro
, and in the more intact nervous system of juvenile rats in arterially perfused brainstem–spinal cord preparations
in situ
. At basal levels of activity, excitation of the respiratory network via simultaneous release of 5-HT and substance P (SP), acting at 5-HT
2A/2C
, 5-HT
4
, and/or neurokinin-1 receptors, was required to maintain inspiratory motor output in both the neonatal and juvenile systems. The midline raphé obscurus contained spontaneously active 5-HT neurons, some of which projected to the pre-BötC and hypoglossal motoneurons, colocalized 5-HT and SP, and received reciprocal excitatory connections from the pre-BötC. Experimentally augmenting raphé obscurus activity increased motor output by simultaneously exciting pre-BötC and motor neurons. Biophysical analyses
in vitro
demonstrated that 5-HT and SP modulated background cation conductances in pre-BötC and motor neurons, including a nonselective cation leak current that contributed to the resting potential, which explains the neuronal depolarization that augmented motor output. Furthermore, we found that 5-HT, but not SP, can transform the electrophysiological phenotype of some pre-BötC neurons to intrinsic bursters, providing 5-HT with an additional role in promoting rhythm generation. We conclude that raphé 5-HT neurons excite key circuit components required for generation of respiratory motor output.
Details
- Title: Subtitle
- Raphé Neurons Stimulate Respiratory Circuit Activity by Multiple Mechanisms via Endogenously Released Serotonin and Substance P
- Creators
- Krzysztof Ptak - Cellular and Systems Neurobiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke–National Institutes of Health, Bethesda, Maryland 20892Tadashi Yamanishi - Cellular and Systems Neurobiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke–National Institutes of Health, Bethesda, Maryland 20892Jason Aungst - Cellular and Systems Neurobiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke–National Institutes of Health, Bethesda, Maryland 20892Lorin S Milescu - Cellular and Systems Neurobiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke–National Institutes of Health, Bethesda, Maryland 20892Ruli Zhang - Cellular and Systems Neurobiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke–National Institutes of Health, Bethesda, Maryland 20892George B Richerson - Departments ofJeffrey C Smith - Cellular and Systems Neurobiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke–National Institutes of Health, Bethesda, Maryland 20892
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.29(12), pp.3720-3737
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.5271-08.2009
- PMID
- 19321769
- PMCID
- PMC2940110
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 03/25/2009
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020636402771
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