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: 10745443
• 负责人: QIAOJIE XIONG
• 金额: $ 6.88万
• 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 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10745443
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease patient; Auditory; Auditory area; Behavior assessment; Corpus striatum structure; Cues; Decision Making; Discrimination; Electrophysiology (science); Frequencies; Goals; Hearing problem; Learning; Mus; Persons; Physiological; Play; Role; Sensory; Synapses; Targeted Research; Thalamic structure; Underrepresented Populations; Work; auditory thalamus; common symptom; graduate student; normal aging; optogenetics; parent grant; sound

The overarching goal of this supplement proposal is to support a new graduate student from underrepresented population, to determine the dysfunctions of the auditory striatum in aging mice and Alzheimer’s disease (AD) mouse lines. Difficulty in learning new tasks and making judgements based on sensory information such as auditory cues are common symptoms in AD patients as well as in normal aging. 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 activity and circuits in aging mice and AD mouse lines, using the approaches and strategies established in the parent grant. First the auditory decision-making and learning deficits in the aging and AD mice will be examined using the auditory frequency discrimination task (cloud-of-tones task) (Aim 1, behavioral assessment), and then tetrode recordings will be used to determine the changes of striatal sound representations in the aging and AD mice (Aim 2, physiological assessment, related to the Aim 1 of the parent grant), finally combination of optogenetic manipulations with electrophysiological recordings will be used to examine the thalamostriatal and corticostriatal synaptic activities in the aging and AD mice (Aim 3, circuit mechanism assessment, related to Aims 1 & 2 of the parent grant).

这个补充建议的首要目标是支持一个新的研究生 从代表性不足的人群，以确定听觉纹状体的功能障碍， 衰老小鼠和阿尔茨海默病（AD）小鼠系。 难以学习新任务并根据感官信息做出判断 例如听觉线索是AD患者以及正常衰老中的常见症状。先前 包括我自己的研究在内的研究表明，听觉纹状体在 听觉决策和学习通过其与听觉丘脑和 皮层在这项提案中，我们将通过确定 听觉纹状体活动和电路在老龄小鼠和AD小鼠线，使用的方法和 父母补助金中制定的策略。 首先，衰老和AD小鼠的听觉决策和学习缺陷将被发现。 使用听觉频率辨别任务（音云任务）检查（Aim1， 行为评估），然后将使用四极管记录来确定 衰老和AD小鼠的纹状体声音表征（目的2，生理评估，相关 达到母基金的目标1），最后将光遗传学操作与 电生理记录将用于检查丘脑纹状体和皮质纹状体 衰老和AD小鼠中的突触活动（目的3，回路机制评估，与 （1）、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19