Gamma frequency entrainment attenuates amyloid load and modifies microglia

Gamma frequency entrainment attenuates amyloid load and modifies microglia

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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 dec...

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Bibliographic Details
Main Authors: Iaccarino, Hannah Frances, Singer, Annabelle, Martorell, Anthony, Rudenko, Andrii, Gao, Fan, Gillingham, Tyler, Mathys, Hansruedi, Seo, Jinsoo, Kritskiy, Oleg, Abdurrob, Fatema, Adaikkan, Chinnakkaruppan, Canter, Rebecca Gail, Rueda IV, Richard, Brown, Emery Neal, Boyden, Edward, Tsai, Li-Huei
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Format: Article
Published: Nature Publishing Group 2017
Online Access:http://hdl.handle.net/1721.1/112229
https://orcid.org/0000-0001-8862-2661
https://orcid.org/0000-0003-4111-1535
https://orcid.org/0000-0002-2206-2590
https://orcid.org/0000-0001-5842-5245
https://orcid.org/0000-0002-1332-6902
https://orcid.org/0000-0003-2668-7819
https://orcid.org/0000-0002-0419-3351
https://orcid.org/0000-0003-1262-0592
Description
Summary: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.

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