A new approach for exploring functional development of fetal brain pathways

Study of functional development of central pathways in fetuses is challenging due to the lack of methods available. In this article, we present a novel approach to test if and when central functional pathways are established by a combination of mapping with c-fos and chronically cannulated fetuses in utero. This approach is based on brain structures such as circumventricular organs (CVOs) that lack the blood-brain barrier (BBB), but are rich in sensors to peripheral signals and contain projections to other brain regions. If signaling molecules in the blood that are too large to cross the BBB induced c-fos expression in both the CVOs and other nuclei inside the fetal brain, this can be evidence that projections from the CVOs to those nuclei are established and functional. This is a useful real-time method to explore the status of functional maturation of pathways between the CVOs and other brain areas in developing fetuses. Notably, at the moment, this is the first and only in vivo method that can detect functional projections in the fetal brain in vitro.