Integration of the thalamic and cortical inputs in the auditory striatum

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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).