Executive functioning-related behavior and neuronal activation in the thalamic nucleus reuniens in a combined...

Fetal Alcohol Spectrum Disorders (FASD) result from prenatal alcohol exposure (AE) and are linked to executive functioning (EF) deficits. The nucleus reuniens (Re) of the thalamus facilitates hippocampal-prefrontal synchrony, essential for EF. While AE alters Re structure and function, its role in EF impairments remains unclear. This study examined the effects of third-trimester equivalent AE on Re volume, neuron count and their activation following a Re-dependent object-in-place (OIP) task in adulthood. Using immunohistochemistry for NeuN (neuronal marker) and ΔFosB (sustained activation marker), we assessed AE-induced changes. We found that AE on postnatal days 4-9 led to reduced Re volume, neuron number, and neuronal activation, as indicated by decreased ΔFosB expression. Behaviorally, AE females showed impaired OIP discrimination, whereas males were unaffected. These findings suggest AE-induced Re dysfunction contributes to EF deficits, particularly in females. Additionally, stress from intubation may influence outcomes and warrants further investigation. This study underscores Re's vulnerability to AE and the need for research into sex-specific mechanisms and interventions for AE-related cognitive deficits.