Impaired sharp-wave ripple coordination between the medial entorhinal cortex and hippocampal CA1 of knock-in model of Alzheimer's disease.
Impaired sharp-wave ripple coordination between the medial entorhinal cortex and hippocampal CA1 of knock-in model of Alzheimer's disease.
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DOI：
10.3389/fnsys.2022.955178
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发表时间：
2022
影响因子：
3
通讯作者：
Igarashi, Kei M.
中科院分区：
文献类型：
--
作者：
Funane, Tsukasa;Jun, Heechul;Sutoko, Stephanie;Saido, Takaomi C.;Kandori, Akihiko;Igarashi, Kei M.
关键词：
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，但其潜在的脑回路机制仍不清楚。在健康的大脑中，海马和内嗅皮层中的尖波波纹（SWR）在记忆巩固中起着关键作用。我们测试了清醒的淀粉样前体蛋白敲入（APP-KI）小鼠MEC层2/3的SWR，同时记录海马CA 1区的SWR。我们发现，先前在健康大脑中发现的SWR的MEC→ CA 1协调在APP-KI小鼠中甚至在空间记忆障碍出现之前的年轻时就被破坏了。有趣的是，在CA 1中，对记忆巩固至关重要的长持续时间SWR轻度减少，尽管SWR密度和振幅保持不变。我们的研究结果表明，在AD记忆障碍之前，内鼻-海马回路中的SWR不协调是一种早期网络症状。
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.
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