Dershowitz Lori B, Bueno Garcia Hassler, Perley Andrew S, Coleman Todd P, Kaltschmidt Julia A
Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
Wu Tsai Neurosciences Institute, Stanford University, Stanford, California, USA.
Neurogastroenterol Motil. 2024 Aug 8:e14890. doi: 10.1111/nmo.14890.
Spontaneous neuronal network activity is essential to the functional maturation of central and peripheral circuits, yet whether this is a feature of enteric nervous system development has yet to be established. Although enteric neurons are known exhibit electrophysiological properties early in embryonic development, no connection has been drawn between this neuronal activity and the development of gastrointestinal (GI) motility patterns.
We use ex vivo GI motility assays with newly developed unbiased computational analyses to identify GI motility patterns across mouse embryonic development.
We find a previously unknown pattern of neurogenic contractions termed "clustered ripples" that arises spontaneously at embryonic day 16.5, an age earlier than any identified mature GI motility patterns. We further show that these contractions are driven by nicotinic cholinergic signaling.
CONCLUSIONS & INFERENCES: Clustered ripples are neurogenic contractile activity that arise from spontaneous ENS activity and precede all known forms of neurogenic GI motility. This earliest motility pattern requires nicotinic cholinergic signaling, which may inform pharmacology for enhancing GI motility in preterm infants.
自发神经元网络活动对于中枢和外周神经回路的功能成熟至关重要,但这是否是肠神经系统发育的一个特征尚未确定。尽管已知肠神经元在胚胎发育早期就表现出电生理特性,但这种神经元活动与胃肠(GI)运动模式的发育之间尚未建立联系。
我们使用新开发的无偏计算分析的离体胃肠运动分析方法,来识别小鼠胚胎发育过程中的胃肠运动模式。
我们发现了一种以前未知的神经源性收缩模式,称为“聚集性波动”,它在胚胎第16.5天自发出现,这一时期比任何已确定的成熟胃肠运动模式都要早。我们进一步表明,这些收缩是由烟碱胆碱能信号驱动的。
聚集性波动是源于肠神经系统自发活动的神经源性收缩活动,先于所有已知形式的神经源性胃肠运动。这种最早的运动模式需要烟碱胆碱能信号,这可能为增强早产儿胃肠动力的药理学提供依据。