Integration of the thalamic and cortical inputs in the auditory striatum

本补充提案的总体目标是确定 阿尔茨海默病小鼠模型的听觉纹状体。阿尔茨海默病（AD）是一种 一种最普遍的严重的与年龄有关的痴呆症，由渐进性死亡引起 神经元的数量。AD的症状包括智力下降， 许多核心的大脑功能，包括记忆，决策和执行功能。到 机械地了解AD的发展，各种AD小鼠模型表达人类 开发了AD转基因。虽然大多数研究集中在分子的变化， 和细胞活动或行为中的认知缺陷，在电路水平上知之甚少， 大脑功能障碍导致AD症状。 难以学习新任务并根据感官信息做出判断 是AD患者的常见症状。以前的研究，包括我自己的工作表明， 听觉纹状体在听觉决策和学习中发挥着重要作用 它与听觉丘脑和皮层的联系。在这份提案中，我们将针对研究 通过确定AD小鼠模型中听觉纹状体回路的功能障碍，J20 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（音云任务），以检查听觉决策- 在J20小鼠中制造和学习缺陷（目标1，行为评估），然后使用 四极录音，以确定J20小鼠纹状体声音表征的变化 (Aim 2，生理评估），最后我们将使用切片电生理记录， 检查J20小鼠中的丘脑纹状体和皮质纹状体突触活动（目的3，电路 机制评估）。

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).