Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer's disease model mice

Nat Neurosci. 2023 Apr;26(4):570-578. doi: 10.1038/s41593-023-01270-2. Epub 2023 Mar 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor
  • Animals
  • Brain / metabolism
  • Disease Models, Animal
  • Hippocampus / metabolism
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism
  • Plaque, Amyloid


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor