Model of Fetal Alcohol Spectrum Disorder

胎儿酒精谱系障碍(FASD)是一个总括术语，用来描述 胎儿期接触酒精(酒精)造成的后果。行为影响可能包括 多动症、注意力缺陷、感觉处理受损、学习和记忆受损 有问题。患有FASD的人也可能在灵活使用信息方面存在困难，这很可能 这是认知缺陷的根源。这样的问题被认为存在于额叶皮质， 包括前额叶皮质。设计新的策略来改善这些问题具有重要的意义 临床相关性。虽然学习和记忆方面的缺陷已经在 对于FASD的啮齿动物模型，我们将检查认知灵活性。我们提出了一种创新的 实验设计给出了产前暴露于中等剂量乙醇的大鼠 胆碱与青春期行为训练。两者中的任何一个都可以改善学习和 正常动物以及FASD模型的记忆。我们已经选择了注意力集合 转换和颠倒学习任务，因为它捕获了在临床观察中报告的缺陷 还因为它可以在相同的大鼠身上重复使用，而不是 可观察到的反应减少或任务策略的变化。我们提出了一个多学科的 一系列将评估行为、大脑功能和结构以及表情的实验 神经代谢物。这些实验将确定是否在过程中调节可塑性 额叶皮质发育可以改善同一动物的记忆和解决问题的能力 以及这些影响是如何在大脑连通性和结构中表现出来的。

Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term used to describe the range of outcomes that result from prenatal exposure to alcohol (ethanol). Behavioral effects may include hyperactivity, attention deficit, impaired sensory processing, and learning and memory problems. People with FASD may also have difficulties using information flexibly which likely underlies deficits in cognition. Such problems are thought to be seated in frontal cortices, including prefrontal cortex. Devising new strategies for amelioration of these problems has great clinical relevance. While deficits in learning and memory have been extensively demonstrated in rodent models of FASD, we will examine cognitive flexibility. We propose an innovative experimental design in which rats exposed to a moderate dose of ethanol prenatally are given choline AND behavioral training during adolescence. Either alone can improve learning and memory in normal animals, as well as in models of FASD. We have chosen the attentional set shifting and reversal learning task because it captures deficits reported in clinical observation of individuals with FASD and also because it can be used repeatedly in the same rats without observable diminution of responding or changes in task strategy. We propose a multidisciplinary set of experiments that will assess behavior, brain function and structure, as well as expression of neurometabolites. These experiments will determine whether modulating plasticity during frontal cortex development can improve both memory and problem solving in the same animals and how the effects manifest in brain connectivity and structure.