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Neuromedin B Expression Defines the Mouse Retrotrapezoid Nucleus
Ist Teil von
The Journal of neuroscience, 2017-11, Vol.37 (48), p.11744-11757
Ort / Verlag
United States: Society for Neuroscience
Erscheinungsjahr
2017
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
The retrotrapezoid nucleus (RTN) consists, by definition, of Phox2b-expressing, glutamatergic, non-catecholaminergic, noncholinergic neurons located in the parafacial region of the medulla oblongata. An unknown proportion of RTN neurons are central respiratory chemoreceptors and there is mounting evidence for biochemical diversity among these cells. Here, we used multiplexed
hybridization and single-cell RNA-Seq in male and female mice to provide a more comprehensive view of the phenotypic diversity of RTN neurons. We now demonstrate that the RTN of mice can be identified with a single and specific marker,
mRNA (
). Most (∼75%) RTN neurons express low-to-moderate levels of
and display chemoreceptor properties. Namely they are activated by hypercapnia, but not by hypoxia, and express proton sensors, TASK-2 and Gpr4. These
-low RTN neurons also express varying levels of transcripts for
,
, and
, and receptors for substance P, orexin, serotonin, and ATP. A subset of RTN neurons (∼20-25%), typically larger than average, express very high levels of
mRNA. These
-high RTN neurons do not express
after hypercapnia and have low-to-undetectable levels of
or
transcripts; they also express
, but are essentially devoid of
and
transcripts. In male rats,
is also a marker of the RTN but, unlike in mice, this gene is expressed by other types of nearby neurons located within the ventromedial medulla. In sum,
is a selective marker of the RTN in rodents;
-low neurons, the vast majority, are central respiratory chemoreceptors, whereas
-high neurons likely have other functions.
Central respiratory chemoreceptors regulate arterial PCO
by adjusting lung ventilation. Such cells have recently been identified within the retrotrapezoid nucleus (RTN), a brainstem nucleus defined by genetic lineage and a cumbersome combination of markers. Using single-cell RNA-Seq and multiplexed
hybridization, we show here that a single marker,
mRNA (
), identifies RTN neurons in rodents. We also suggest that >75% of these
neurons are chemoreceptors because they are strongly activated by hypercapnia and express high levels of proton sensors (
and
). The other RTN neurons express very high levels of
, but low levels of
, and do not respond to hypercapnia. Their function is unknown.