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

基本信息

批准号：
10579975
负责人：
Padmashri Ragunathan
金额：
$ 27.11万
依托单位：
CREIGHTON UNIVERSITY
依托单位国家：
美国
项目类别：
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/10579975
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 receptor expression receptor function trafficking

项目摘要

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.

项目概要/摘要怀孕期间接触酒精会导致胎儿酒精谱系障碍 (FASD) 伴有感觉和认知缺陷。患有 FASD 的人听觉处理受损，并且经常表现出非典型的听觉行为。发育时期的酒精暴露已被证明会导致发育障碍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，目前对于酒精对 AMPAR 的影响如何改变突触的理解还存在差距。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 产前暴露小鼠模型来研究听觉障碍的机制。 FASD 中观察到的加工缺陷。我们将检查产前暴露于酒精，在初级听觉皮层进行体内成像，以追踪 AMPAR 和树突棘数天，并进行电生理记录以研究 AMPAR 介导的突触传递。的目标建议为 FASD 中观察到的听觉处理改变提供机制基础并检查 BDNF 模拟物 7,8-二羟基黄酮在保护或恢复中枢听觉方面的治疗潜力胎儿酒精暴露后的处理。