Lability of neuronal lineage decisions is revealed by acute exposures to ethanol

Developing neurons pass through periods of sensitivity to environmental factors, e.g., alterations induced by ethanol are defined when the exposure occurs. We tested the hypothesis that timely episodic prenatal exposure to ethanol can change the lineage of cortical neurons. This study exploited mice in which many layer V neurons expressed a Thy1-YFPh transgene and endogenously fluoresced yellow. Fetuses were exposed to ethanol or saline on gestational day (G) 14 (when layer V neurons were generated) or on G 15 or 17 (when these layer V neurons were migrating). Fetuses dosed on G 14 exhibited an increased frequency of YFP+ neurons across cortex. This contrasted with a decreased frequency following ethanol exposure on G 17. Ethanol did not affect overall density of layer V neurons or their generation. Thus, the magnitude and valence of ethanol-induced changes in YFP+ neurons are time-dependent. Cell lineage is defined at the time of origin and the window of lability for this definition continues into the early post-mitotic (migratory) period.