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).

该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 最常见的严重与年龄相关的痴呆症，由进行性死亡引起 广泛的大脑区域的神经元。 AD 的症状包括智力下降，影响 许多核心大脑功能，包括记忆、决策和执行功能。到 机械地了解AD的发展，表达人类的各种AD小鼠模型 AD 转基因被开发出来。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，在电路水平上我们知之甚少 大脑功能障碍会导致 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，包括我自己的作品表明， 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。在本提案中，我们将针对研究 通过确定 AD 小鼠模型 J20 中听觉纹状体回路的功能障碍来确定间隙 转基因小鼠，使用为父母资助建立的方法。我们将首先使用 听觉频率辨别任务（音调云任务）来检查听觉决策- J20 小鼠的制造和学习缺陷（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 （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 小鼠的丘脑纹状体和皮质纹状体突触活动（目标 3，电路 机制评估）。