Integration of the thalamic and cortical inputs in the auditory striatum

这项补充提案的首要目标是支持一名新的研究生。 从代表不足的人群中，来确定听觉纹状体的功能障碍 衰老小鼠和阿尔茨海默病(AD)小鼠品系。 学习新任务和根据感官信息做出判断的困难 像听觉提示这样的症状在AD患者和正常衰老中都很常见。上一首 包括我自己的作品在内的研究表明，听觉纹状体在 听觉决策和学习通过其与听觉丘脑和 大脑皮层。在这项提案中，我们将通过确定 老年小鼠和AD小鼠品系中的听觉纹状体活动和回路 在父母资助中确立的战略。 首先，衰老和AD小鼠的听觉决策和学习障碍 使用听觉频率辨别任务(音调云任务)进行检查(目标1， 行为评估)，然后将使用四极管记录来确定 衰老和阿尔茨海默病小鼠的纹状体声音表现(目标2，生理学评估，相关 到父母赠款的目标1)，最后将光遗传操作与 电生理记录将用于检查丘脑纹状体和皮质纹状体 衰老和阿尔茨海默病小鼠的突触活动(目标3，电路机制评估，与 目标是父母补助金的1和2)。

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).