Integration of the thalamic and cortical inputs in the auditory striatum

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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).