UC San Diego

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive mnemonic deficits. Previous studies have established that AD causes neural dysfunction in hippocampal place cells in the form of decreased place cell stability and increased place field size in mouse models. Most such experiments, however, have been unable to record from specific layers of the hippocampus while mouse models complete goal-oriented spatial memory tasks. Here, we introduced a spatial memory task to allow electrophysiology recordings from the CA1, CA3, and DG regions of the hippocampus while transgenic AD mouse models completed the task. We also aimed to develop calcium imaging to analyze populations of place cells from the CA1 region and we hoped to compare data retrieved using calcium imaging to data acquired from tetrode wire electrophysiology. We found that CA1 and CA3 place cells showed impairments in firing rate, information score, and stability, while showing increased spatial correlation and place field size while animals completed hippocampal dependent memory tasks, particularly as animals got older. While our calcium imaging experiments were unsuccessful, we set the foundation for future calcium imaging experiments in this research. Our results thus point towards substantial CA1 and CA3 place cell dysfunction while AD mouse models complete hippocampal dependent spatial memory tasks. Furthermore, our experiments set the stage for using calcium imaging as method that can add to previously existing information about place cell dysfunction in AD and paint a more global image of hippocampal dysfunction in AD.