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Frequency and duration of sensory flicker control transcriptional profiles in 5xFAD mice
Sara Bitarafan, Alyssa F Pybus, Felix G Rivera Moctezuma
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA.
Abstract:
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.
Insights
Audiovisual flicker stimulation impacts brain gene expression. Different frequencies and durations affect immune, synaptic, and metabolic genes in brain regions relevant to Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Gamma frequency sensory stimulation is being explored for Alzheimer's disease (AD) treatment.
- Previous research indicated that visual flicker stimulation influences signaling pathways in the mouse visual cortex.
- Understanding the broad transcriptional effects of audiovisual (AV) flicker stimulation is crucial.
Purpose of the Study:
- To investigate the transcriptional effects of different frequencies and durations of AV flicker stimulation on brain functions.
- To determine how AV flicker stimulation impacts gene expression in brain regions affected by AD.
Main Methods:
- Mice were exposed to varying frequencies and durations of AV flicker stimulation.
- Transcriptional changes in the visual cortex and hippocampus were analyzed.
Main Results:
- AV flicker stimulation rapidly activated immune genes in the visual cortex (VC) across all tested frequencies.
- Synaptic genes were suppressed in the VC after prolonged stimulation.
- In the hippocampus, 20 Hz AV flicker upregulated genes related to mitochondrial function, metabolism, and synaptic translation.
- 10 Hz AV flicker suppressed genes associated with neurotransmitter activity in the hippocampus.
Conclusions:
- The frequency and duration of AV flicker stimulation are critical determinants of its effects on gene expression.
- AV flicker stimulation modulates immune, neuronal, and metabolic genes in brain regions relevant to Alzheimer's disease.
- These findings provide insights into the molecular mechanisms underlying sensory stimulation therapies for AD.
