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Published on: May 3, 2017
Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer's disease model mice
Marisol Soula1, Alejandro Martín-Ávila2,3, Yiyao Zhang1
1Neuroscience Institute, Langone Medical Center, New York University, New York, NY, USA.
Abstract:
There is a demand for noninvasive methods to ameliorate disease. We investigated whether 40-Hz flickering light entrains gamma oscillations and suppresses amyloid-β in the brains of APP/PS1 and 5xFAD mouse models of Alzheimer's disease. We used multisite silicon probe recording in the visual cortex, entorhinal cortex or the hippocampus and found that 40-Hz flickering simulation did not engage native gamma oscillations in these regions. Additionally, spike responses in the hippocampus were weak, suggesting 40-Hz light does not effectively entrain deep structures. Mice avoided 40-Hz flickering light, associated with elevated cholinergic activity in the hippocampus. We found no reliable changes in plaque count or microglia morphology by either immunohistochemistry or in vivo two-photon imaging following 40-Hz stimulation, nor reduced levels of amyloid-β 40/42. Thus, visual flicker stimulation may not be a viable mechanism for modulating activity in deep structures.
Insights
Investigating 40-Hz flickering light for Alzheimer's disease (AD), this study found it did not entrain brain gamma oscillations or reduce amyloid-beta plaques in mouse models. The light was avoided by mice, indicating it may not be a viable noninvasive AD therapy.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Gerontology
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques.
- Noninvasive methods to ameliorate AD are in high demand.
- Gamma oscillations are implicated in cognitive function and AD pathology.
Purpose of the Study:
- To investigate if 40-Hz flickering light can entrain gamma oscillations in the brain.
- To determine if 40-Hz light stimulation reduces amyloid-beta burden in AD mouse models.
- To assess the efficacy of visual flicker stimulation for modulating neural activity in deep brain structures.
Main Methods:
- Multisite silicon probe recordings in the visual cortex, entorhinal cortex, and hippocampus of APP/PS1 and 5xFAD mice.
- Immunohistochemistry and in vivo two-photon imaging to analyze plaque count and microglia morphology.
- Measurement of amyloid-beta 40/42 levels.
- Assessment of mouse behavior and cholinergic activity.
Main Results:
- 40-Hz flickering light did not engage native gamma oscillations in the studied brain regions.
- Spike responses in the hippocampus were weak, indicating poor entrainment of deep structures.
- Mice exhibited avoidance of 40-Hz light, correlated with elevated hippocampal cholinergic activity.
- No significant reduction in plaque count, altered microglia morphology, or decreased amyloid-beta levels were observed.
Conclusions:
- 40-Hz flickering light stimulation is not effective in entraining gamma oscillations or reducing amyloid-beta pathology in these AD mouse models.
- The observed behavioral avoidance and lack of deep brain structure engagement suggest limitations for this noninvasive approach.
- Visual flicker stimulation may not be a viable therapeutic strategy for modulating deep brain activity or treating Alzheimer's disease.
