TY - JOUR
T1 - Gamma frequency entrainment attenuates amyloid load and modifies microglia
AU - Iaccarino, Hannah F.
AU - Singer, Annabelle C.
AU - Martorell, Anthony J.
AU - Rudenko, Andrii
AU - Gao, Fan
AU - Gillingham, Tyler Z.
AU - Mathys, Hansruedi
AU - Seo, Jinsoo
AU - Kritskiy, Oleg
AU - Abdurrob, Fatema
AU - Adaikkan, Chinnakkaruppan
AU - Canter, Rebecca G.
AU - Rueda, Richard
AU - Brown, Emery N.
AU - Boyden, Edward S.
AU - Tsai, Li Huei
N1 - Publisher Copyright:
© 2016 Macmillan Publishers Limited, part of Springer Nature.
PY - 2016/12/7
Y1 - 2016/12/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85014113371&partnerID=8YFLogxK
U2 - 10.1038/nature20587
DO - 10.1038/nature20587
M3 - Article
C2 - 27929004
AN - SCOPUS:85014113371
SN - 0028-0836
VL - 540
SP - 230
EP - 235
JO - Nature
JF - Nature
IS - 7632
ER -