Optogenetic gamma stimulation rescues memory impairments in an Alzheimer's disease mouse model.,Nature Communications

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Optogenetic gamma stimulation rescues memory impairments in an Alzheimer's disease mouse model.
Nature Communications ( IF 14.7 ) Pub Date : 2019-11-22 , DOI: 10.1038/s41467-019-13260-9
Guillaume Etter ₁ , Suzanne van der Veldt ₁ , Frédéric Manseau ₁ , Iman Zarrinkoub ₁ , Emilie Trillaud-Doppia ₁ , Sylvain Williams ₁

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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.

中文翻译：

光遗传学γ刺激可以挽救阿尔茨海默氏病小鼠模型中的记忆障碍。

缓慢的伽马振荡（30-60 Hz）与空间记忆的检索有关。在阿尔茨海默氏病中观察到改变的慢伽马振荡。在这里，我们使用J20-APP AD鼠标模型，该模型显示空间内存损耗以及降低的慢伽马幅值和耦合到theta振荡相位的相位幅值。为了恢复海马中的伽马振荡，我们使用光遗传学以不同的频率激活内侧间隔小白蛋白神经元。我们表明光遗传刺激小白蛋白神经元在40赫兹（但不是80赫兹）恢复海马慢伽马振荡振幅，和J20 AD小鼠模型的相位-振幅耦合。尽管有明显的斑块沉积，恢复过程中缓慢的伽马振荡的恢复仍能挽救小鼠的空间记忆。

更新日期：2019-11-22

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