Developmental dynamics of prepiriform cortex in prenatal human ontogenesis

The prepiriform cortex is a part of the phylogenetically oldest pallial division (paleocortex) representing the primary olfactory cortex. While olfactory centers in laboratory animals have been extensively investigated, the developmental timetable of the human prepiriform area is poorly understood. Thus, in the present study we aim to examine the prepiriform cortex in human fetuses from eight postconceptional weeks to birth. Based on cytoarchitecture and immunohistochemistry analysis (NeuN-, SYP-, NSE-, TH-, GFAP-, MBP-) four main periods of the prepiriform cortex fetal development are suggested: the beginning of prefetal stage (the eighth week from conception), the period from the ending of prefetal stage (9-12 postconceptional weeks) to 17 weeks of gestation, 18-27 weeks of gestation and the late fetal period (29-40 gestational weeks). We found that the initial layer differentiation took place before the ninthtenth weeks from conception and by ten weeks the paleocortical plate of the prepiriform cortex was shaped. Both total cell density and NeuN-immunoreactive cell density peaked in the early fetuses and started to decrease after 17 gestational weeks, attaining intermediate values at 18-27 weeks and becoming significantly lower in the late fetuses. In contrast, the NeuN-immunoreactive cell ratio gradually increased over the whole examined period. The prepiriform cortex was defined as approaches the state at birth at 30 gestational weeks. The same developmental periods were observed with SYP- and NSE-assays. No significant distribution of TH immunoreactivity was described in the prepiriform cortex of human fetuses. The prior paleocortex development was demonstrated using glial markers: GFAPimmunoreactivity appeared in the prepiriform cortex at the middle of the early fetal period, ahead of the neocortex and insular cortex. The earlier rates of GFAP-immunoreactivity expansion in the prepiriform cortex, as compared to other pallial regions, persisted in the later fetuses. The first MBP-immunoreactive fibres within pallium were detected in the lateral olfactory tract at 30 weeks. Therefore, the prepiriform cortex approaches a level of maturation similar to that at birth already at the beginning of the late fetal period and matures prior to other pallial regions.