Funane Tsukasa, Jun Heechul, Sutoko Stephanie, Saido Takaomi C, Kandori Akihiko, Igarashi Kei M
Center for Exploratory Research, Hitachi, Ltd., Kokubunji, Japan.
Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, United States.
Front Syst Neurosci. 2022 Aug 25;16:955178. doi: 10.3389/fnsys.2022.955178. eCollection 2022.
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.
临床证据表明，内嗅皮层是引发阿尔茨海默病（AD）记忆障碍的主要脑区，但潜在的脑回路机制仍不清楚。在健康大脑中，海马体和内嗅皮层中的尖波涟漪（SWRs）在记忆巩固中起关键作用。我们测试了清醒的淀粉样前体蛋白敲入（APP-KI）小鼠内侧内嗅皮层（MEC）2/3层中的SWRs，并与海马体CA1区的SWRs同时进行记录。我们发现，之前在健康大脑中发现的MEC→CA1的SWRs协调性，在APP-KI小鼠中被破坏，即使在空间记忆障碍出现之前的幼年时期也是如此。有趣的是，尽管SWR密度和振幅保持不变，但对记忆巩固至关重要的长时间SWRs在CA1区略有减少。我们的研究结果表明，内嗅-海马回路中的SWR不协调是AD记忆障碍之前出现的一种早期网络症状。
