Moderate prenatal alcohol exposure alters the number and function of GABAergic interneurons in the murine orbitofrontal cortex.

Exposure to alcohol during development produces Fetal Alcohol Spectrum Disorders (FASD), characterized by a wide range of effects that include deficits in multiple cognitive domains. Early identification and treatment of individuals with FASD remain a challenge because neurobehavioral alterations do not become a significant problem until late childhood and early adolescence. Understanding the mechanisms underlying low and moderate prenatal alcohol exposure (PAE) effects on behavior and cognition is essential for improved diagnosis and treatment. Here, we examined the functional and morphological changes in an area known to be involved in executive control, the orbitofrontal cortex (OFC). We found that a moderate PAE model, previously shown to impair behavioral flexibility and to alter OFC activity in vivo, produced moderate functional and morphological changes within the OFC of mice in vitro. Specifically, slice electrophysiological recordings of spontaneous inhibitory post-synaptic currents in OFC pyramidal neurons revealed a significant increase in the amplitude and area in PAE mice relative to controls. Immunohistochemistry uncovered an increase in calretinin-, but not somatostatin- or parvalbumin-expressing cortical interneurons in the OFC of PAE mice. Together, these data suggest that moderate prenatal alcohol exposure alters the disinhibitory function in the OFC, which may contribute to the executive function deficits associated with FASD.