Optogenetic gamma stimulation rescues memory impairments in an Alzheimer's disease mouse model
Optogenetic gamma stimulation rescues memory impairments in an Alzheimer's disease mouse model
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DOI：
10.1038/s41467-019-13260-9
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发表时间：
2019-11-22
影响因子：
16.6
通讯作者：
Williams, Sylvain
中科院分区：
文献类型：
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作者：
Etter, Guillaume;van der Veldt, Suzanne;Williams, Sylvain
缓慢的伽马振荡（30-60赫兹）与空间记忆的检索相关。在阿尔茨海默病中观察到改变的慢伽马振荡。在这里，我们使用J20-APP AD小鼠模型，显示空间记忆丧失以及缓慢的伽马振幅和相位振幅耦合到θ振荡相位的减少。为了恢复海马的伽马振荡，我们使用光遗传学在不同频率激活内侧间隔小白蛋白神经元。我们发现，40 Hz（而不是80 Hz）光遗传刺激小白蛋白神经元可以恢复J20 AD小鼠模型的海马慢伽马振荡振幅和相位振幅耦合。尽管有明显的斑块沉积，但恢复小鼠空间记忆时的慢伽马振荡。这些结果支持慢伽马振荡在记忆中的作用，并表明40 Hz光遗传刺激内间隔小白蛋白神经元可能为治疗AD患者的记忆缺陷提供一种新的策略。
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.