Effects of Prenatal Alcohol Exposure on Synaptic Plasticity and Auditory Processing

项目摘要/摘要 怀孕期间接触酒精会导致胎儿酒精谱系障碍(FASD)，这与 有感觉和认知缺陷。患有FASD的个体听觉处理能力受损，还经常 表现出非典型的听觉行为。已有研究表明，发育期酒精暴露会导致脑损伤 神经元可塑性包括树突棘的减少和AMPA受体(AMPAR)功能的改变。 然而，目前在了解酒精对AMPAR的影响如何改变突触方面存在差距 完整大脑的可塑性以及AMPAR运输的变化如何导致听觉处理的改变。 在这里，我们将使用一种产前暴露的FASD小鼠模型来研究听觉机制。 在FASD中观察到加工缺陷。我们将研究胎儿期暴露的小鼠的听觉过程 酒精，在初级听觉皮质进行活体成像，以跟踪AMPAR和树突刺数天， 并进行电生理记录，以研究AMPAR介导的突触传递。的目标是 建议为FASD中观察到的改变的听觉处理提供机制基础并检查 脑源性神经营养因子类似物7，8-二羟基黄酮对中枢听觉保护或恢复的治疗作用 胎儿酒精暴露后的处理。

PROJECT SUMMARY/ABSTRACT Exposure to alcohol during pregnancy produces fetal alcohol spectrum disorders (FASD) that are associated with sensory and cognitive deficits. Individuals with FASD have impaired auditory processing and also frequently exhibit atypical auditory behaviors. Developmental alcohol exposure has been shown to cause impairments in neuronal plasticity including reduction in dendritic spines and alterations in AMPA receptor (AMPAR) function. However, currently there is a gap in understanding how the effects of alcohol on AMPARs alters synaptic plasticity in the intact brain and how changes in AMPAR trafficking can result in alterations in auditory processing. Here, we will use a prenatal exposure mouse model of FASD to investigate the mechanism of auditory processing deficits observed in FASD. We will examine auditory processing in mice prenatally exposed to alcohol, perform in vivo imaging in the primary auditory cortex to track AMPARs and dendritic spines over days, and perform electrophysiological recordings to study AMPAR-mediated synaptic transmission. The goal of the proposal is to provide a mechanistic basis for the altered auditory processing observed in FASD and examine the therapeutic potential of the BDNF mimetic 7,8-Dihydroxy flavone to preserve or restore central auditory processing following fetal alcohol exposure.