Integration of the thalamic and cortical inputs in the auditory striatum

NIH RePORTER · NIH · R01 · $323,698 · view on reporter.nih.gov ↗

Abstract

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).

Key facts

NIH application ID
10285092
Project number
3R01DC017470-03S1
Recipient
STATE UNIVERSITY NEW YORK STONY BROOK
Principal Investigator
QIAOJIE XIONG
Activity code
R01
Funding institute
NIH
Fiscal year
2021
Award amount
$323,698
Award type
3
Project period
2019-02-10 → 2024-01-31