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Optogenetic gamma stimulation rescues memory impairments in an Alzheimer’s disease mouse model

Author

Listed:
  • Guillaume Etter

    (McGill University & Douglas Mental Health University Institute)

  • Suzanne van der Veldt

    (McGill University & Douglas Mental Health University Institute)

  • Frédéric Manseau

    (McGill University & Douglas Mental Health University Institute)

  • Iman Zarrinkoub

    (McGill University & Douglas Mental Health University Institute)

  • Emilie Trillaud-Doppia

    (McGill University & Douglas Mental Health University Institute)

  • Sylvain Williams

    (McGill University & Douglas Mental Health University Institute)

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.

Suggested Citation

  • Guillaume Etter & Suzanne van der Veldt & Frédéric Manseau & Iman Zarrinkoub & Emilie Trillaud-Doppia & Sylvain Williams, 2019. "Optogenetic gamma stimulation rescues memory impairments in an Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13260-9
    DOI: 10.1038/s41467-019-13260-9
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    Cited by:

    1. Bálint Király & Andor Domonkos & Márta Jelitai & Vítor Lopes-dos-Santos & Sergio Martínez-Bellver & Barnabás Kocsis & Dániel Schlingloff & Abhilasha Joshi & Minas Salib & Richárd Fiáth & Péter Barthó , 2023. "The medial septum controls hippocampal supra-theta oscillations," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    2. Panna Hegedüs & Bálint Király & Dániel Schlingloff & Victoria Lyakhova & Anna Velencei & Írisz Szabó & Márton I. Mayer & Zsofia Zelenak & Gábor Nyiri & Balázs Hangya, 2024. "Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Guillaume Etter & Suzanne Veldt & Jisoo Choi & Sylvain Williams, 2023. "Optogenetic frequency scrambling of hippocampal theta oscillations dissociates working memory retrieval from hippocampal spatiotemporal codes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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