Corticostriatal Circuit Models of Cognitive Impairments Induced by Fetal Exposure to Alcohol.

The term Fetal Alcohol Spectrum Disorder (FASD) includes a group of diseases caused by fetal alcohol exposure (FAE). FASD patients display heterogenous socio-emotional and cognitive deficits, particularly in the domain of executive function, which share symptoms with other neuropsychiatric disorders. Despite the availability of several preclinical models, the developmental brain defects causally linked to behavioral deficits induced by FAE remain poorly understood. Here, we first review the effects of FAE on corticostriatal development and its impact on both corticostriatal pathway function and cognitive abilities. We propose three non-mutually exclusive circuit models of corticostriatal dysfunctions to account for some of the FAE-induced cognitive deficits. One model posits that associative-sensorimotor imbalance causes hyper goal-directed behavior and a second model implies that alteration of prefrontal-striatal behavioral suppression circuits results in loss of behavioral inhibition. A third model suggests that local striatal circuit deficits affect striatal neuronal ensemble function to impair action selection and performance. Finally, we discuss how pre-clinical approaches applied to these circuit models could offer potential rescue strategies for executive function deficits in FASD patients.

胎儿酒精谱系障碍（FASD）这一术语包括一组由胎儿酒精暴露（FAE）引起的疾病。FASD患者表现出不同的社会情感和认知缺陷，特别是在执行功能方面，其症状与其他神经精神疾病有相似之处。尽管有几种临床前模型可用，但与FAE导致的行为缺陷有因果关系的发育性大脑缺陷仍未被充分了解。在此，我们首先回顾了FAE对皮质纹状体发育的影响及其对皮质纹状体通路功能和认知能力的影响。我们提出了三种非相互排斥的皮质纹状体功能障碍回路模型，以解释一些由FAE引起的认知缺陷。一种模型假定联想 - 感觉运动失衡导致过度的目标导向行为，第二种模型意味着前额叶 - 纹状体行为抑制回路的改变导致行为抑制的丧失。第三种模型表明局部纹状体回路缺陷影响纹状体神经元集群功能，从而损害动作选择和执行。最后，我们讨论了应用于这些回路模型的临床前方法如何为FASD患者的执行功能缺陷提供潜在的挽救策略。