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Impaired sharp-wave ripple coordination between the medial entorhinal cortex and hippocampal CA1 of knock-in model of Alzheimer’s disease

Clinical evidence suggests that the entorhinal cortex is a primary brain area triggering memory impairments in Alzheimer’s disease (AD), but the underlying brain circuit mechanisms remain largely unclear. In healthy brains, sharp-wave ripples (SWRs) in the hippocampus and entorhinal cortex play a cr...

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Detalles Bibliográficos
Autores principales: Funane, Tsukasa, Jun, Heechul, Sutoko, Stephanie, Saido, Takaomi C., Kandori, Akihiko, Igarashi, Kei M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9452631/
https://www.ncbi.nlm.nih.gov/pubmed/36090186
http://dx.doi.org/10.3389/fnsys.2022.955178
Descripción
Sumario:Clinical evidence suggests that the entorhinal cortex is a primary brain area triggering memory impairments in Alzheimer’s disease (AD), but the underlying brain circuit mechanisms remain largely unclear. In healthy brains, sharp-wave ripples (SWRs) in the hippocampus and entorhinal cortex play a critical role in memory consolidation. We tested SWRs in the MEC layers 2/3 of awake amyloid precursor protein knock-in (APP-KI) mice, recorded simultaneously with SWRs in the hippocampal CA1. We found that MEC→CA1 coordination of SWRs, found previously in healthy brains, was disrupted in APP-KI mice even at a young age before the emergence of spatial memory impairments. Intriguingly, long-duration SWRs critical for memory consolidation were mildly diminished in CA1, although SWR density and amplitude remained intact. Our results point to SWR incoordination in the entorhinal-hippocampal circuit as an early network symptom that precedes memory impairment in AD.