Diversity Supplement for Hector Zepeda: Gamma Sensory Flicker to Induce Resilient Brain Immune Function Mr. Hector Zepeda, the trainee in this proposal, will lead a new project related to but distinct from Aim 1 of the parent grant. This project provides enhanced training to Mr. Zepeda, a graduate student from an under-represented group in science. Microglia, the brain's primary immune cells, are thought to play a causal role in the risk of developing AD, the most prevalent type of dementia. According to recent research by the parent grant's principal investigator, Dr. Singer, neuronal electrical activity at 40Hz frequency alters microglia phenotype and cytokine expression. Because of its potential to modulate the phenotype of microglia, flicker stimulation is a promising early intervention in AD. However, the effects of flicker in a preclinical stage are unknown. Thus, this project will determine how flicker affects microglia and astrocytes in mice that express ApoE4, the major genetic risk factor for AD. ApoE4 drives microglia into a reactive or overly active state that ultimately leads to synapses loss and neurodegeneration. In the presence of an immune challenge and ApoE4, microglia enter a perpetual reactive state and with limited ability to enter less reactive states. The aim for this project is to determine how to use flicker stimulation to mitigate this reactive microglia and astrocyte responses in the face of an immune challenge. Mr. Zepeda will test the central hypothesis that flicker promotes resilience in brain immune cells, such that these cells become less reactive to immune challenges. Promising results from this research project will provide the foundation to use flicker as a preclinical therapy for persons susceptible to Alzheimer's disease due to ApoE4 expression. During this project, Mr. Zepeda will undergo enhanced training in animal models of Alzheimer’s disease, glia responses to neural activity, and neuroimmune function in health and Alzheimer’s disease with close mentorship of Drs. Annabelle Singer and Levi Wood.