title: Gamma frequency entrainment attenuates amyloid load and modifies microglia.
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)1-40and Aβ1-42isoforms. 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 Aβ1-40and Aβ1-42levels 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.
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Hunter F
authors.initials: HF
authors.lastname: Iaccarino
authors.affiliation: McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|MIT Media Lab, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Annabelle C
authors.initials: AC
authors.lastname: Singer
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Martorell
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Andrii
authors.initials: A
authors.lastname: Rudenko
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Gao
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Tyler Z
authors.initials: TZ
authors.lastname: Gillingham
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Hansruedi
authors.initials: H
authors.lastname: Mathys
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Seo
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Kritskiy
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Fatema
authors.initials: F
authors.lastname: Abdurrob
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Chinnakkaruppan
authors.initials: C
authors.lastname: Adaikkan
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Canter
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Rueda
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Institute of Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Massachusetts General Hospital, Boston, Massachusetts, Massachusetts 02114, USA.
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.affiliation: McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|MIT Media Lab, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Boyden
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02139, USA.
authors.forename: Li-Huei
authors.initials: LH
authors.lastname: Tsai
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D065818:Gamma Rhythm / Q000528:radiation effects; D007395:Interneurons / Q000378:metabolism / Q000528:radiation effects; D008027:Light; D008297:Male; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D062308:Optogenetics; D010320:Parvalbumins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000517:prevention & control* / Q000628:therapy; D059467:Transcriptome; D014793:Visual Cortex / Q000502:physiology / Q000528:radiation effects
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010320:Parvalbumins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)