Developmental alcohol exposure: Impacts on medial prefrontal cortex morphology and the excitatory-inhibitory balance

Alcohol is one of the most commonly used substances during pregnancy and adolescence, two of the most vulnerable periods of cognitive development. The prefrontal cortex (PFC) is a cortical region of the frontal lobe involved in various complex executive functions that are affected by alcohol exposure. Specifically, the medial prefrontal cortex (mPFC), a subregion of the PFC, performs critical roles in cognitive processing, such as conditioned fear, reward-seeking, impulse control, working memory, and pain. The mPFC begins developing in utero and continues to mature into adulthood. Thus, it is particularly vulnerable to drug exposures during both gestation and adolescence. Clinical and preclinical research have explored the impact of Fetal Alcohol Spectrum Disorders (FASD) and Alcohol Use Disorder (AUD) on the PFC. However, how prenatal and adolescent alcohol exposure affect the mPFC and its specific subregions remains underexplored. This review focuses on the mPFC subregion and its involvement in two key developmental periods affected by alcohol exposure: gestation and adolescence. Both prenatal alcohol exposure (PAE) and adolescent alcohol exposure disrupt the morphology and excitatory-inhibitory balance of the mPFC, which results in long-lasting functional and behavioral consequences. This review emphasizes the importance of investigating subregion-specific alterations in the mPFC following developmental alcohol exposure and calls for further research into the effects of PAE, adolescent alcohol exposure, or the combination of both on mPFC development.