Third trimester-equivalent alcohol exposure reduces neurons in males and increases Vglut2+ neurons with reduced intrinsic bursting in females in the murine dorsal subiculum.

Individuals with Fetal Alcohol Spectrum Disorders (FASDs) show reduced subicular volume, and preclinical studies complement this by demonstrating that third-trimester-equivalent ethanol exposure induces apoptosis in corticolimbic regions, including the subiculum. The subiculum mediates hippocampal-cortical communication critical for long-term memory consolidation. Within the distal dorsal subiculum, a population of bursting neurons uniquely expresses VGLUT2 and plays a key role in memory processing. We hypothesized that third-trimester-equivalent ethanol exposure would reduce neuronal and VGLUT2+ cell density in the dorsal subiculum and reduce the excitability of bursting neurons, providing a mechanism for long-term memory impairments observed in FASD. To test this, postnatal day (P) 7 mice received subcutaneous injections of ethanol, and long-term effects were assessed in adolescence (P35-62). Using transgenic mice with fluorescently labeled VGLUT2+ neurons and immunohistochemistry, we observed a significant reduction in neuronal density in males and an increase in VGLUT2+ cell density in females. Using whole-cell patch-clamp electrophysiology, we observed a reduction in the number of action potentials per burst in both sexes. Additionally, females showed reduced overall excitability, and a subset of neurons exhibited a shift to regular spiking. These findings suggest that developmental ethanol exposure disrupts subicular output by impairing burst firing, potentially weakening hippocampal-cortical communication and contributing to the cognitive deficits associated with FASD.