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Deep brain stimulation of thalamic nucleus reuniens promotes neuronal and cognitive resilience in an Alzheimer’s disease mouse model

Author

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  • Shiri Shoob

    (Faculty of Medicine, Tel Aviv University)

  • Nadav Buchbinder

    (Faculty of Medicine, Tel Aviv University
    Tel Aviv University)

  • Ortal Shinikamin

    (Faculty of Medicine, Tel Aviv University)

  • Or Gold

    (The Hebrew University of Jerusalem)

  • Halit Baeloha

    (Faculty of Medicine, Tel Aviv University)

  • Tomer Langberg

    (Faculty of Medicine, Tel Aviv University
    Tel Aviv University)

  • Daniel Zarhin

    (Faculty of Medicine, Tel Aviv University)

  • Ilana Shapira

    (Faculty of Medicine, Tel Aviv University)

  • Gabriella Braun

    (Faculty of Medicine, Tel Aviv University
    Tel Aviv University)

  • Naomi Habib

    (The Hebrew University of Jerusalem)

  • Inna Slutsky

    (Faculty of Medicine, Tel Aviv University
    Tel Aviv University)

Abstract

The mechanisms that confer cognitive resilience to Alzheimer’s Disease (AD) are not fully understood. Here, we describe a neural circuit mechanism underlying this resilience in a familial AD mouse model. In the prodromal disease stage, interictal epileptiform spikes (IESs) emerge during anesthesia in the CA1 and mPFC regions, leading to working memory disruptions. These IESs are driven by inputs from the thalamic nucleus reuniens (nRE). Indeed, tonic deep brain stimulation of the nRE (tDBS-nRE) effectively suppresses IESs and restores firing rate homeostasis under anesthesia, preventing further impairments in nRE-CA1 synaptic facilitation and working memory. Notably, applying tDBS-nRE during the prodromal phase in young APP/PS1 mice mitigates age-dependent memory decline. The IES rate during anesthesia in young APP/PS1 mice correlates with later working memory impairments. These findings highlight the nRE as a central hub of functional resilience and underscore the clinical promise of DBS in conferring resilience to AD pathology by restoring circuit-level homeostasis.

Suggested Citation

  • Shiri Shoob & Nadav Buchbinder & Ortal Shinikamin & Or Gold & Halit Baeloha & Tomer Langberg & Daniel Zarhin & Ilana Shapira & Gabriella Braun & Naomi Habib & Inna Slutsky, 2023. "Deep brain stimulation of thalamic nucleus reuniens promotes neuronal and cognitive resilience in an Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42721-5
    DOI: 10.1038/s41467-023-42721-5
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    1. Denise J. Cai & Daniel Aharoni & Tristan Shuman & Justin Shobe & Jeremy Biane & Weilin Song & Brandon Wei & Michael Veshkini & Mimi La-Vu & Jerry Lou & Sergio E. Flores & Isaac Kim & Yoshitake Sano & , 2016. "A shared neural ensemble links distinct contextual memories encoded close in time," Nature, Nature, vol. 534(7605), pages 115-118, June.
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