Integration of the thalamic and cortical inputs in the auditory striatum

听觉纹状体中丘脑和皮质输入的整合

• 批准号: 10285092
• 负责人: QIAOJIE XIONG
• 金额: $ 32.37万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-10 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10285092
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease patient; Auditory; Auditory area; Behavior; Behavior assessment; Brain; Brain region; Cognitive deficits; Corpus striatum structure; Decision Making; Dementia; Development; Discrimination; Electrophysiology (science); Frequencies; Goals; Hearing problem; Human; J20 mouse; Lead; Learning; Memory; Molecular; Physiological; Play; Psyche structure; Role; Sensory; Slice; Symptoms; Synapses; Targeted Research; Thalamic structure; Transgenes; Transgenic Mice; Work; age related; auditory thalamus; base; brain dysfunction; common symptom; executive function; mouse model; neuron loss; parent grant; sound

The overarching goal of this supplement proposal is to determine the dysfunctions of the auditory striatum in an Alzheimer’s disease mouse model. Alzheimer’s disease (AD) is the most prevalent form of serious age-related dementia, which is produced by progressive death of neurons in a wide range of brain regions. Symptoms of AD involve mental decline that affects many core brain functions including memory, decision-making, and executive function. To mechanistically understand the AD development, various AD mouse models expressing human AD transgenes were developed. While most studies focusing on either the changes of molecular and cellular activities or the cognitive deficits in behaviors, little is known at circuitry level how the brain dysfunctions lead to AD symptoms. Difficulty in learning new tasks and making judgements based on sensory information are common symptoms in AD patients. Previous studies including my own works indicated that the auditory striatum plays an essential role in auditory decision-making and learning through its connections with auditory thalamus and cortex. In this proposal, we will target the research gap by determining the dysfunction of auditory striatal circuits in an AD mouse model, J20 transgenic mouse, using the approaches established for the parent grant. We will first use the auditory frequency discrimination task (cloud-of-tones task) to examine the auditory decision- making and learning deficits in the J20 mice (Aim 1, behavioral assessment), and then use tetrode recordings to determine the changes of striatal sound representations in the J20 mice (Aim 2, physiological assessment), finally we will use slice electrophysiological recording to examine the thalamostriatal and corticostriatal synaptic activities in the J20 mice (Aim 3, circuit mechanism assessment).

这项补充提案的首要目标是确定 阿尔茨海默病小鼠模型中的听觉纹状体。阿尔茨海默病(AD)是 最常见的严重老年性痴呆，由渐进性死亡引起 大范围大脑区域的神经元。阿尔茨海默病的症状包括智力下降，影响 许多核心的大脑功能，包括记忆、决策和执行功能。至 从机制上理解AD的发展，各种AD小鼠模型表达人类 已开发出AD转基因。虽然大多数研究都集中在分子的变化上 以及细胞活动或行为中的认知缺陷，在电路水平上如何 大脑功能障碍会导致阿尔茨海默病症状。 学习新任务和根据感官信息做出判断的困难 是AD患者的常见症状。之前的研究，包括我自己的作品，都表明 听觉纹状体在听觉决策和学习中起着重要作用。 它与听觉丘脑和皮质的联系。在这项提案中，我们将针对研究 通过测定AD小鼠模型J20中听觉纹状体回路的功能障碍来确定GAP 转基因小鼠，使用为父母赠款建立的方法。我们将首先使用 听觉频率辨别任务(音调云任务)，以检查听觉决定- 在J20小鼠中制造和学习障碍(目标1，行为评估)，然后使用 四极管记录法测定J20小鼠纹状体声音表征的变化 (目标2，生理评估)，最后我们将使用切片电生理记录来 检查J20小鼠丘脑纹状体和皮质纹状体的突触活动(目标3，回路 机制评估)。