Effects of Prenatal Alcohol Exposure on Synaptic Plasticity and Auditory Processing

产前酒精暴露对突触可塑性和听觉处理的影响

• 批准号: 10364618
• 负责人: Padmashri Ragunathan
• 金额: $ 30.63万
• 依托单位: CREIGHTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-05 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364618
• 关键词: AMPA Receptors; Acoustics; Affect; Agonist; Animal Model; Auditory; Auditory Brainstem Responses; Auditory Evoked Potentials; Auditory area; Autopsy; Behavior; Brain; Brain-Derived Neurotrophic Factor; Cells; Central Auditory Processing Disorder; Child; Cognitive deficits; Communities; Dendritic Spines; Development; Electrophysiology (science); Exhibits; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal alcohol effects; Flavones; Goals; Hearing; Human; Impairment; Individual; Measures; Mediating; Mus; Neuronal Plasticity; Neurons; Neurotrophic Tyrosine Kinase Receptor Type 2; PHluorin; Prevalence; Reporting; Role; Sensorineural Hearing Loss; Sensory; Signal Transduction; Startle Reaction; Structure; Synapses; Synaptic Transmission; Synaptic plasticity; Testing; Therapeutic; Vertebral column; alcohol consumption during pregnancy; alcohol effect; alcohol exposure; auditory deprivation; auditory processing; hearing impairment; in vivo; in vivo imaging; mimetics; mouse model; otoacoustic emission; patch clamp; prenatal exposure; prepulse inhibition; preservation; receptor; trafficking

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.

项目摘要/摘要 怀孕期间暴露于酒精会产生相关的胎儿酒精谱系（FASD） 有感觉和认知缺陷。 FASD患者的听觉处理受损，并且经常 表现出非典型的听觉行为。发育性酒精暴露已被证明会导致损害 神经元可塑性，包括减少树突状刺和AMPA受体（AMPAR）功能的改变。 但是，当前了解酒精对Ampars的影响如何改变突触存在差距 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FASD的产前暴露鼠标模型来研究听觉的机理 在FASD中观察到的处理缺陷。我们将检查在暴露于产前的小鼠中的听觉处理 酒精，在主要听觉皮层中进行体内成像，以跟踪几天的AMPAR和树突状刺 并执行电生理记录以研究AMPAR介导的突触传播。目标的目标 提案是为在FASD中观察到的更改的听觉处理提供机械基础并检查 BDNF模拟7,8-二羟基黄酮的治疗潜力以保存或恢复中央听觉 胎儿酒精暴露后处理。