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Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587.

Gamma frequency entrainment attenuates amyloid load and modifies microglia.

Author information

1
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
2
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
3
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
4
MIT Media Lab, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
5
Institute of Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
6
Massachusetts General Hospital, Boston, Massachusetts, Massachusetts 02114, USA.
7
Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02139, USA.

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.

PMID:
27929004
PMCID:
PMC5656389
DOI:
10.1038/nature20587
[Indexed for MEDLINE]
Free PMC Article

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