Understanding Brain Networks Causing Associative Memory Impairments in AD
To determine the time course of associative memory cell impairment in APP-KI mice, I will implant a 64-channel recording drive carrying 16 tetrodes and record from LEC cells of APP-KI mice across two age groups. To determine if optogenetic stimulation of DA neurons restores associative memory in APP-KI mice, I will first test whether APP-KI mice exhibit reward-associated dopamine signals in the LEC as observed in WT mice using fiber photometry. I will further test whether optogenetic stimulation of LEC dopaminergic fibers improves associative memory of APP-KI mice.
We are one of the only few labs studying circuit mechanisms underlying associative memory in the lateral entorhinal cortex, and presumably the first lab that focuses on the associative memory impairment in AD. Our lab has all experimental setups for the proposed in vivo electrophysiological recording and an associative learning behavioral paradigm. The proposed study represents high innovation because these systems neuroscience-oriented methods have not been applied in the AD research field. My research will help us identify target neural circuits to prevent progression of AD and to slow or mitigate the progression of associative memory impairments in AD patients. Our results may also lead to the future development of effective circuit-based therapeutics applicable to preserve or improve memory function in AD patients, including brain reactivation using deep-brain stimulation.