Optogenetic gamma stimulation rescues memory impairments in an Alzheimer's disease mouse model
Guillaume Etter,Suzanne van der Veldt,Frédéric Manseau,Iman Zarrinkoub,Emilie Trillaud-Doppia,Sylvain Williams +5 more
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TL;DR: Results support the role of slow gamma oscillations in memory and suggest that optogenetic stimulation of medial septal parvalbumin neurons at 40 Hz could provide a novel strategy for treating memory deficits in AD.
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Abstract: Slow gamma oscillations (30–60 Hz) correlate with retrieval of spatial memory. Altered slow gamma oscillations have been observed in Alzheimer’s disease. Here, we use the J20-APP AD mouse model that displays spatial memory loss as well as reduced slow gamma amplitude and phase-amplitude coupling to theta oscillations phase. To restore gamma oscillations in the hippocampus, we used optogenetics to activate medial septal parvalbumin neurons at different frequencies. We show that optogenetic stimulation of parvalbumin neurons at 40 Hz (but not 80 Hz) restores hippocampal slow gamma oscillations amplitude, and phase-amplitude coupling of the J20 AD mouse model. Restoration of slow gamma oscillations during retrieval rescued spatial memory in mice despite significant plaque deposition. These results support the role of slow gamma oscillations in memory and suggest that optogenetic stimulation of medial septal parvalbumin neurons at 40 Hz could provide a novel strategy for treating memory deficits in AD. Slow gamma oscillations are associated with memory and have been reported to be disrupted in patients with Alzheimer’s disease. Here the authors show that optogenetic stimulation of medial septum parvalbumin neurons at 40 Hz rescues memory retrieval in the J20 mouse model of Alzheimer’s disease.
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Citations
Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies
Diane Chan,Ho-Jun Suk,Brennan Jackson,Noah Milman,Danielle Stark,Elizabeth B. Klerman,Erin G. Kitchener,Vanesa S. Fernandez Avalos,Gabrielle de Weck,Arit Banerjee,Sara D. Beach,Joel W. Blanchard,Colton Stearns,Aaron D. Boes,Brandt D. Uitermarkt,Phillip E. Gander,Matthew A. Howard,Eliezer J. Sternberg,Alfonso Nieto-Castañon,Sheeba Arnold Anteraper,Susan Whitfield-Gabrieli,Emery N. Brown,Edward S. Boyden,Bradford C. Dickerson,Li-Huei Tsai +24 more
TL;DR: In this article , a non-invasive Gamma ENtrainment using Sensory Stimulation (GENUS) at 40Hz was shown to reduce Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevent cerebral atrophy, and improve behavioral testing performance in mouse models of AD.
Slow Wave Sleep Is a Promising Intervention Target for Alzheimer's Disease
Yee Fun Lee,Yee Fun Lee,Dmitry Gerashchenko,Igor Timofeev,Brian J. Bacskai,Ksenia V. Kastanenka +5 more
TL;DR: Since SWA disruptions occur prior to the plaque deposition,SWA disruptions may provide an early biomarker for AD and it is proposed that therapeutic targeting of SWA in AD might lead to an effective treatment for Alzheimer’s patients.
Rhythmic light flicker rescues hippocampal low gamma and protects ischemic neurons by enhancing presynaptic plasticity.
Zheng Lifeng,Yu Mei,Rui Lin,Yunxuan Wang,Zhan Zhuo,Ning Cheng,Mengzhen Wang,Yongqiang Tang,Liping Wang,Hou Shengtao +9 more
TL;DR: Modulation of low-gamma oscillations using a light flicker can restore low gamma oscillations and protect ischemic neurons and support a causal relationship between CA1 slow gamma and cognitive dysfunctions in the isChemic brain.
The role of gamma oscillations in central nervous system diseases: Mechanism and treatment
Ao Guan,Shaoshuang Wang,Ailing Huang,Chenyue Qiu,Yansong Li,Xuying Li,Jinfei Wang,Qiang Wang,Bin Deng +8 more
TL;DR: This review discusses the function of gamma oscillations in advanced brain activities from both a physiological and pathological standpoint, and it emphasizes gamma entrainment as a potential therapeutic approach for a range of neuropsychiatric diseases.
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Anti-ApoE Antibody Given after Plaque Onset Decreases Aβ Accumulation and Improves Brain Function in a Mouse Model of Aβ Amyloidosis
Fan Liao,Yukiko Hori,Eloise Hudry,Adam Q. Bauer,Hong Jiang,Thomas E. Mahan,Katheryn B. Lefton,Tony J. Zhang,Joshua T. Dearborn,Jungsu Kim,Joseph P. Culver,Rebecca A. Betensky,David F. Wozniak,Bradley T. Hyman,David M. Holtzman +14 more
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