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Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model

机译:敲入阿尔茨海默病模型内侧内嗅皮层的体内伽马振荡受损。

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摘要

The entorhinal cortex (EC) has bidirectional connections with the hippocampus and plays a critical role in memory formation and retrieval. EC is one of the most vulnerable regions in the brain in early stages of Alzheimer’s disease (AD), a neurodegenerative disease with progressive memory impairments. Accumulating evidence from healthy behaving animals indicates gamma oscillations (30–100 Hz) as critical for mediating interactions in the circuit between EC and hippocampus. However, it is still unclear whether gamma oscillations have causal relationship with memory impairment in AD. Here we provide the first evidence that in vivo gamma oscillations in the EC are impaired in an AD mouse model. Cross-frequency coupling of gamma (30–100 Hz) oscillations to theta oscillations was reduced in the medial EC of anesthetized amyloid precursor protein knock-in (APP-KI) mice. Phase locking of spiking activity of layer II/III pyramidal cells to the gamma oscillations was significantly impaired. These data indicate that the neural circuit activities organized by gamma oscillations were disrupted in the medial EC of AD mouse model, and point to gamma oscillations as one of possible mechanisms for cognitive dysfunction in AD patients.
机译:内嗅皮层(EC)与海马具有双向连接,并且在记忆形成和恢复中起关键作用。 EC是阿尔茨海默氏病(AD)早期大脑中最脆弱的区域之一,AD是一种具有进行性记忆障碍的神经退行性疾病。来自健康的行为动物的越来越多的证据表明,伽马振荡(30-100 Hz)对于介导EC和海马之间回路的相互作用至关重要。但是,尚不清楚伽马振荡是否与AD的记忆障碍有因果关系。在这里,我们提供了第一个证据,即AD小鼠模型中EC中的体内伽马振荡受到损害。在麻醉的淀粉样蛋白前体蛋白敲入(APP-KI)小鼠的内侧EC中,γ(30-100 Hz)振荡与θ振荡的跨频耦合降低。 II / III层锥体细胞对伽马振荡的尖峰活动的锁相被大大削弱。这些数据表明,由γ振荡组织的神经回路活动在AD小鼠模型的内侧EC中被破坏,并指出γ振荡是AD患者认知功能障碍的可能机制之一。

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