Gamma frequency entrainment attenuates amyloid load and modifies microglia

Hunter F. Iaccarino, Annabelle C. Singer, Anthony J. Martorell, Andrii Rudenko, Fan Gao, Tyler Z. Gillingham, Hansruedi Mathys, Jinsoo Seo, Oleg Kritskiy, Fatema Abdurrob, Chinnakkaruppan Adaikkan, Rebecca G. Canter, Richard Rueda, Emery N. Brown, Edward S. Boyden and Li-Huei Tsai ()
Additional contact information
Hunter F. Iaccarino: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Annabelle C. Singer: McGovern Institute for Brain Research, Massachusetts Institute of Technology
Anthony J. Martorell: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Andrii Rudenko: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Fan Gao: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Tyler Z. Gillingham: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Hansruedi Mathys: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Jinsoo Seo: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Oleg Kritskiy: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Fatema Abdurrob: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Chinnakkaruppan Adaikkan: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Rebecca G. Canter: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Richard Rueda: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Emery N. Brown: Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Edward S. Boyden: McGovern Institute for Brain Research, Massachusetts Institute of Technology
Li-Huei Tsai: Picower Institute for Learning and Memory, Massachusetts Institute of Technology

Nature, 2016, vol. 540, issue 7632, 230-235

Abstract: 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)1–40 and Aβ 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 Aβ1–40 and Aβ1–42 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.

Date: 2016
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DOI: 10.1038/nature20587

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