Increased hippocampal seizure susceptibility in FASD
Fetal alcohol spectrum disorders (FASD) - is common term used to describes the range of adverse developmental outcomes that may occur in a person whose mother drank alcohol during pregnancy. FASD is associated with several comorbidities including epilepsy. Seizures are observed with a frequency of 3–21% in children with FASD. The mechanisms underlying epileptic phenomena associated with FASD are not fully understood. Here, we show increased excitability in hippocampal slices of the rats during the second postnatal week following single exposure to ethanol and identify the impairments in GABAergic inhibition that are likely involved in this increased excitability. Using extracellular recordings we observed that hippocampal slices prepared from the P7-9 rats 12 hours following alcohol exposure (6 g/kg, i.p.) display clonic-like and tonic-clonic seizure like activity during exposure to elevated extracellular potassium (6 mM) much more frequently than slices prepared from the control animals. Whole-cell recordings from CA3/CA4 pyramidal cells revealed strong reduction in the frequency of the GABAergic postsynaptic currents, without any change in their amplitude and kinetics, in slices from the ethanol-exposed animals. In parallel experiments in GAD-GFP P7-9 mice, we observed massive apoptosis, revealed with cleaved caspase-3 staining, in the hippocampal interneurons twelve hours following alcohol exposure. Thus, death of hippocampal interneurons following alcohol exposure may lead to impairments in GABAergic inhibition and increased seizure excitability in FASD.