The prevalence of convenience-driven delivery via Caesarian-section (C-section) has been steadily increasing in Western as well as in developing societies. Today, significantly more deliveries occur via surgical means than medical necessity mandates. Despite tremendous advances in surgical techniques and pre- and post-operative surgical care, there remains to be limited understanding on the physiological influence of vaginal birth with particular emphasis on long term outcome on the offspring. Serendipitously, we recently uncovered in mice that vaginal birth induces significantly higher level of Ucp2 mRNA expression in the hippocampus than experimental C-section. We showed that during the early postnatal period, UCP2 expression promotes neuronal differentiation, axonal outgrowth and synapse formation in the hippocampus. We also observed that Ucp2 knockout animals show adult behaviors associated with the hippocampal formation that is different from wild type littermates. Taken together these observations suggest that vaginal birth may play a crucial role in determining adult brain structure and function that is different from that of the effect of surgically assisted birth.