Alcohol in Neocortex Development and Plasticity

摘要 患有胎儿酒精谱系障碍（FASD）的儿童通常会出现感觉改变，例如 对同时出现的多种感官刺激的厌恶，注意力缺陷，视觉运动能力差 整合，并破坏一般感觉处理。越来越多的证据支持这样一种观点， 这些问题引起社会问题和学习缺陷。因此，了解 在不同感觉方式的加工过程中，发育性酒精暴露对于设计 干预措施，以改善FASD中出现的神经行为问题。多感觉整合（MSI）是一个更高的 顺序功能，其中来自两个或多个感觉模态的输入的组合导致或促进 或抑制神经元反应。MSI依赖于个体感觉系统的精确布线， 然后是这些系统向多感觉处理区域收敛的准确性。这种精度是 通过活动依赖性神经元可塑性过程获得，包括连接的发芽和修剪。 在人类大脑皮层中，这些可塑性变化大多发生在人类妊娠的第三个三个月。 已知乙醇会严重影响皮质中的活动依赖性神经元可塑性。我们的总体 一种假说认为，发育过程中的酒精暴露破坏了大脑皮层的功能和结构连接， 多感觉皮质区改变MSI并导致FASD中的神经行为损伤。在 在这里提出的研究中，我们将使用先进的成像技术的组合;体内电生理学 和一种新的离体切片制备，以评估发育期酒精暴露对 多感觉皮质区的结构、功能和电生理特性。此外，我们将测试 增强活动依赖性神经元可塑性是否会逆转酒精对多感觉神经元的影响， 处理.这些实验的完成将作出重大和范式转变的贡献 FASD研究领域。

Abstract Children with fetal alcohol spectrum disorders (FASD) often present sensory alterations such as aversion to multiple sensory stimuli presented at the same time, attention deficits, poor visual-motor integration, and disrupted general sensory processing. There is growing evidence supporting the idea that these problems give rise to social problems and learning deficits. Therefore, understanding the effects of developmental alcohol exposure in the processing of different sensory modalities is crucial to devise interventions to ameliorate neurobehavioral problems seen in FASD. Multisensory integration (MSI) is a higher order function in which the combination of inputs from two or more sensory modalities leads to either facilitation or suppression of neuronal responses. MSI relies on the precise wiring of the individual sensory systems and then on the accuracy of convergence of these systems to multisensory processing areas. This precision is acquired by activity-dependent neuronal plasticity processes that include sprouting and pruning of connections. In the human cortex, most of these plastic changes occur during the third trimester of human gestation. Ethanol is known to severely affect activity-dependent neuronal plasticity in the cortex. Our overarching hypothesis is that alcohol exposure during development disrupts the functional and structural connectivity of multisensory cortical areas altering MSI and contributing to neurobehavioral impairments in FASD. In the studies proposed here we will use a combination of advanced imaging techniques; in vivo electrophysiology and a novel ex vivo slice preparation to evaluate the effect of developmental alcohol exposure on the structural, functional and electrophysiological properties of multisensory cortical areas. Moreover we will test whether boosting activity-dependent neuronal plasticity would reverse the effects of alcohol on multisensory processing. The accomplishment of these experiments will make a major and paradigm-shifting contribution towards the FASD research field.