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

• DOI: 10.3389/fnsys.2022.955178
• Publication Date: 2022-08-25T04:28:28Z
• Authors: Tsukasa Funane; Heechul Jun; Stephanie Sutoko; Takaomi C. Saido; Akihiko Kandori; Kei M. Igarashi
• Keywords: 0301 basic medicine; 03 medical and health sciences; entorhinal cortex; hippocampus; medial entorhinal cortex (MEC); Neurosciences. Biological psychiatry. Neuropsychiatry; Alzheimer’s disease; sharp-wave ripples (SWRs); RC321-571; Neuroscience

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.