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变化，如 对同时出现的多种感觉刺激的厌恶，注意力缺陷，视觉运动能力差 整合，并扰乱了一般的感觉处理。越来越多的证据支持这样一种观点 这些问题引发了社会问题和学习障碍。因此，了解 在不同感觉模式的加工过程中，发育性酒精暴露是设计 改善FASD神经行为问题的干预措施。多感官整合(MSI)是一种更高的 来自两个或多个感官通道的输入的组合导致任一促进的顺序功能 或抑制神经元反应。MSI依赖于各个感官系统的精确连接 然后讨论这些系统收敛到多感官处理区域的准确性。这个精度是 通过依赖活动的神经元可塑性过程获得，包括发芽和修剪连接。 在人类大脑皮层，这些可塑性变化大多发生在人类怀孕的第三个三个月。 众所周知，乙醇会严重影响大脑皮层中依赖活动的神经元的可塑性。我们最重要的是 假说是发育过程中的酒精暴露会破坏大脑功能和结构的连通性 多感觉皮层区域改变MSI并导致FASD的神经行为损害。在 这里提出的研究我们将使用先进的成像技术相结合；活体电生理学 以及一种新的体外切片制剂，以评估发育性酒精暴露对 多感觉皮层区域的结构、功能和电生理特性。此外，我们还将测试 增强活动依赖的神经元可塑性是否会逆转酒精对多感官的影响 正在处理。这些实验的完成将做出重大的、改变范式的贡献 向FASD研究领域迈进。

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.