Gamma frequency entrainment attenuates amyloid load and modifies microglia
Author(s)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; ... Show more Show less
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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 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.
DepartmentInstitute for Medical Engineering and 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
Nature Publishing Group
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
Author's final manuscript