Learning and Memory
Learning and Memory
5 years ago

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
Guillaume Etter, Suzanne van der Veldt, Frédéric Manseau, Iman Zarrinkoub, Emilie Trillaud-Doppia, Sylvain Williams
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.

Publisher URL: https://www.nature.com/articles/s41467-019-13260-9

Open URL: https://doi.org/10.1038/s41467-019-13260-9

DOI: 10.1038/s41467-019-13260-9

Open access
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