Different impacts on brain function depending on the mode of delivery

•Atp1a2−/− neonates showed life or death phenotype depending the mode of delivery.•Mode of deliveries affected the levels of monoamines and proteins in neonatal brains.•Mice showed different behaviors in adulthood depending on the mode of delivery.•Results indicate that birth modes influence on functional neural network formation. The prevalence of delivery through cesarean-section (C-section) has been increasing worldwide. Although different modes of delivery, such as vaginal birth and C-section, are associated with incidence of some diseases in humans, little is known about how delivery stimuli affect short- and long-term brain function. Phenotypic analyses of Atp1a2 homozygous knockout (Atp1a2−/−) neonates showed that the mode of delivery affected neural phenotypes; Atp1a2−/− mice born by vaginal delivery started spontaneous breathing, while Atp1a2−/− mice born by C-section showed a complete absence of breathing followed by their death. This life or death phenotype prompted us to examine several aspects of the neonatal brain following C-section or vaginal delivery. We found significantly different levels of several monoamines and transporters/channel proteins and a different c-Fos expression pattern. Furthermore, these mice showed different behaviors in adulthood. Our results suggest that birth mode impacts neurotransmission and functional network formation in the neonatal brain.