Gamma frequency entrainment attenuates amyloid load and modifies microglia
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Author(s)
Iaccarino, Hannah Frances
Singer, Annabelle
Martorell, Anthony
Rudenko, Andrii
Gao, Fan
Gillingham, Tyler
Mathys, Hansruedi
Seo, Jinsoo
Kritskiy, Oleg
Abdurrob, Fatema
Date Issued
December 2016
Journal
Nature
Publisher
Nature Publishing Group
Citation
Iaccarino, Hannah F. et al. “Gamma Frequency Entrainment Attenuates Amyloid Load and Modifies Microglia.” Nature 540, 7632 (December 2016): 230–235 © 2016 Macmillan Publishers Limited, part of Springer Nature
Version
Author's final manuscript
Abstract
Changes in gamma oscillations (20-50 Hz) have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies is unclear. Here we show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer's disease. Optogenetically driving fast-spiking parvalbumin-positive (FS-PV)-interneurons at gamma (40 Hz), but not other frequencies, reduces levels of amyloid-β (Aβ)[subscript 1-40] and Aβ [subscript 1-42] isoforms. Gene expression profiling revealed induction of genes associated with morphological transformation of microglia, and histological analysis confirmed increased microglia co-localization with Aβ. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced Aβ[subscript 1-40] and Aβ[subscript 1-42] levels in the visual cortex of pre-depositing mice and mitigated plaque load in aged, depositing mice. Our findings uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer's-disease-associated pathology.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Media Laboratory
McGovern Institute for Brain Research at MIT
Picower Institute for Learning and Memory
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/NATURE20587
