Developmental ethanol exposure produces deficits in long‐term potentiation in vivo that persist following postnatal choline supplementation

• Published in: Alcohol, clinical & experimental research clinical & experimental research, 2024-08, Vol.48 (8), p.1483-1491
• Main Authors: Titterness, A. K., Gräfe, E. L., Acosta, C., Rodriguez, C., Thomas, J. D., Christie, B. R.
• Format: Article
• Language: English
• Subjects: dentate gyrus; developmental ethanol exposure; postnatal choline supplementation; sex differences; synaptic plasticity
• ISSN: 2993-7175; 2993-7175
• DOI: 10.1111/acer.15384

Background Fetal alcohol spectrum disorder (FASD) is one of the leading causes of neurodevelopmental disorder for which there is a pressing need for an effective treatment. Recent studies have investigated the essential nutrient choline as a postnatal treatment option. Supplementation with choline has produced improvements in behavioral tasks related to learning and memory and reverted changes in methylation signature following third‐trimester equivalent ethanol exposure. We examined whether there are related improvements in hippocampal synaptic plasticity in vivo. Methods Sprague–Dawley offspring were administered binge‐levels of ethanol from postnatal day (PND) 4 to 9, then treated with choline chloride (100 mg/kg/day) from PND 10 to 30. In vivo electrophysiology was performed on male and female offspring from PND 55 to 70. Long‐term potentiation (LTP) was induced in the medial perforant pathway of the dentate gyrus using a theta‐burst stimulation (TBS) protocol, and field‐evoked postsynaptic potentials (EPSPs) were evoked for 60 min following the conditioning stimulus. Results Developmental ethanol exposure caused long‐lasting deficits in LTP of the slope of the evoked responses and in the amplitude of the population spike potentiation. Neither deficit was rescued by postnatal choline supplementation. Conclusions In contrast to our prior findings that choline can improve hippocampal plasticity (Nutrients, 2022, 14, 2004), here we found that deficits in hippocampal synaptic plasticity due to developmental ethanol exposure persisted into adulthood despite adolescent choline supplementation. Future research should examine more subtle changes in synaptic plasticity to identify synaptic changes that mirror behavioral improvements. This work found that third‐trimester ethanol exposure produced long‐lasting deficits in hippocampal synaptic plasticity in adult animals (greater than postnatal day 50) that were not rescued by postnatal choline supplementation early in life (postnatal day 10–30). These results indicate that longer periods of supplementation may be required to produce more persistent benefits.