Transcriptomes of electrophysiologically recorded Dbx1-derived respiratory neurons of the preBötzinger complex in neonatal mice.

Transcriptomes of electrophysiologically recorded Dbx1-derived respiratory neurons of the preBötzinger complex in neonatal mice.
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DOI:
10.1038/s41598-022-06834-z
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发表时间:
2022-02-21
期刊:
影响因子:
4.6
通讯作者:
Del Negro CA
Del Negro CA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kallurkar PS;Picardo MCD;Sugimura YK;Saha MS;Conradi Smith GD;Del Negro CA

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呼吸依赖于来自Dbx 1表达前体的前BötC复合体中的中间神经元。在这里,我们调查是否节奏和模式生成功能驻留在离散类Dbx 1 preBötC神经元。在一个约5 s周期的呼吸切片模型中,肺节律性1型Dbx 1 preBötC神经元在2型神经元之前100-300 ms激活,肺专门用于输出模式,在吸气运动输出之前300-500 ms激活。我们对1型和2型转录组进行了测序,并确定了123个基因的差异表达,包括离子型受体(Gria 3,Gabra 1),这可能解释了它们的吸气前激活谱和参与吸气和叹气爆发的Ca 2+信号传导(Cracr 2a,Sgk 1)。令人惊讶的是,影响呼吸的神经肽受体(例如,μ-阿片和蛙皮素样肽受体)仅稀疏表达,这表明同源肽和阿片类药物对preBötC核心的一小部分发挥了深远的影响。这些公共领域的数据有助于解释呼吸的神经起源。
Breathing depends on interneurons in the preBötzinger complex (preBötC) derived from Dbx1-expressing precursors. Here we investigate whether rhythm- and pattern-generating functions reside in discrete classes of Dbx1 preBötC neurons. In a slice model of breathing with ~ 5 s cycle period, putatively rhythmogenic Type-1 Dbx1 preBötC neurons activate 100–300 ms prior to Type-2 neurons, putatively specialized for output pattern, and 300–500 ms prior to the inspiratory motor output. We sequenced Type-1 and Type-2 transcriptomes and identified differential expression of 123 genes including ionotropic receptors (Gria3, Gabra1) that may explain their preinspiratory activation profiles and Ca2+ signaling (Cracr2a, Sgk1) involved in inspiratory and sigh bursts. Surprisingly, neuropeptide receptors that influence breathing (e.g., µ-opioid and bombesin-like peptide receptors) were only sparsely expressed, which suggests that cognate peptides and opioid drugs exert their profound effects on a small fraction of the preBötC core. These data in the public domain help explain the neural origins of breathing.
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