Frequency and duration of sensory flicker control transcriptional profiles in 5xFAD mice

Current clinical trials are investigating gamma frequency sensory stimulation as a potential therapeutic strategy for Alzheimer's disease (AD); yet, we lack a comprehensive picture of the effects of this stimulation on multiple aspects of brain function. We previously showed that exposing mice to visual flickering stimulation increased mitogen activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cells signaling in the visual cortex (VC) in a manner dependent on the duration and frequency of stimulation. Because these pathways control multiple neuronal and glial functions, here we aimed to define the transcriptional effects of different frequencies and durations of audiovisual flicker (AV flicker) stimulation on multiple brain functions. Within the VC, we found that all stimulation frequencies caused fast activation of a module of immune genes within 0.5 h and slower suppression of synaptic genes after 4 h. In the hippocampus, we found that a 20 Hz AV flicker activated a module of genes associated with mitochondrial function, metabolism, and synaptic translation, while 10 Hz rapidly suppressed a module of genes linked to neurotransmitter activity. Collectively, our data indicate that the frequency and duration of AV flicker stimulation control immune, neuronal, and metabolic genes in multiple regions of the brain affected by AD.