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.

在发育过程中接触酒精会产生胎儿酒精谱系障碍 (FASD)，其特点是影响范围广泛，包括多个认知领域的缺陷。FASD 患者的早期识别和治疗仍然是一个挑战，因为神经行为改变直到儿童晚期和青春期早期才成为一个重大问题。了解低度和中度产前酒精暴露 (PAE) 对行为和认知影响的潜在机制对于改进诊断和治疗至关重要。在这里，我们检查了一个已知参与执行控制的区域，即眶额皮质 (OFC) 的功能和形态变化。我们发现中度 PAE 模型，以前显示会损害行为灵活性并改变体内OFC 活动，在体外小鼠的 OFC 中产生了适度的功能和形态变化。具体而言，OFC 锥体神经元中自发抑制性突触后电流的切片电生理记录显示，与对照组相比，PAE 小鼠的振幅和面积显着增加。免疫组织化学发现 PAE 小鼠的 OFC 中表达钙视网膜蛋白的皮质中间神经元增加，但没有增加表达生长抑素或小清蛋白的皮质中间神经元。总之，这些数据表明，适度的产前酒精暴露会改变 OFC 的去抑制功能，这可能导致与 FASD 相关的执行功能缺陷。