Alzheimer's disease (AD) is pathologically characterized by amyloid-β (Aβ) accumulation, which induces Aβ-dependent neuronal dysfunctions. We focused on the early-stage disease progression and examined the neuronal network functioning in the 5xFAD mice. The simultaneous intracranial recordings were obtained from the hippocampal perforant path (PP) and the dentate gyrus (DG). Concomitant to Aβ accumulation, theta power was strongly attenuated in the PP and DG regions of 5xFAD mice compared to those in nontransgenic littermates. For either theta rhythm or gamma oscillation, the phase synchronization on the PP-DG pathway was impaired, evidenced by decreased phase locking value and diminished coherency index. To alleviate the neural oscillatory deficits in early-stage AD, a neural modulation approach (rTMS) was used to activate gamma oscillations and strengthen the synchronicity of neuronal activity on the PP-DG pathway. In brief, there was a significant neuronal network dysfunction at an early-stage AD-like pathology, which preceded the onset of cognitive deficits and was likely driven by Aβ accumulation, suggesting that the neural oscillation analysis played an important role in early AD diagnosis.

中文翻译：

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海马θ和伽马振荡的早期功能障碍及其对转基因 5xFAD 小鼠模型中神经网络的调节

阿尔茨海默病 (AD) 的病理学特征是淀粉样蛋白 β (Aβ) 积累，这会导致 Aβ 依赖性神经元功能障碍。我们专注于早期疾病进展并检查了 5xFAD 小鼠的神经元网络功能。同时从海马穿孔通路（PP）和齿状回（DG）获得颅内记录。随着 Aβ 积累，与非转基因同窝仔鼠相比，5xFAD 小鼠的 PP 和 DG 区域的 theta 功率显着减弱。对于 theta 节律或 gamma 振荡，PP-DG 通路上的相位同步受损，这可以通过锁相值降低和相干指数降低来证明。为了减轻早期 AD 的神经振荡缺陷，神经调制方法 (rTMS) 用于激活伽马振荡并加强 PP-DG 通路上神经元活动的同步性。简而言之，在早期 AD 样病理学中存在显着的神经元网络功能障碍，这在认知缺陷发生之前并且可能由 Aβ 积累驱动，表明神经振荡分析在早期 AD 诊断中发挥了重要作用。