Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model.
Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model.
复制标题
DOI：
10.3389/fnsys.2017.00048
复制
发表时间：
2017
影响因子：
3
通讯作者：
Igarashi KM
中科院分区：
文献类型：
--
作者：
Nakazono T;Lam TN;Patel AY;Kitazawa M;Saito T;Saido TC;Igarashi KM
内嗅皮层（EC）与海马体具有双向连接，在记忆形成和检索中发挥着关键作用。 EC 是阿尔茨海默病 (AD) 早期阶段大脑中最脆弱的区域之一，阿尔茨海默病是一种具有进行性记忆障碍的神经退行性疾病。来自健康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 和海马体之间回路的相互作用至关重要。然而，目前尚不清楚伽马振荡是否与 AD 记忆障碍有因果关系。在这里，我们提供了第一个证据，证明 AD 小鼠模型中 EC 体内伽马振荡受到损害。在麻醉淀粉样前体蛋白敲入 (APP-KI) 小鼠的内侧 EC 中，γ (30–100 Hz) 振荡与 theta 振荡的交叉频率耦合减少。 II/III 层锥体细胞的尖峰活动与伽马振荡的锁相显着受损。这些数据表明，在AD小鼠模型的内侧EC中，由伽马振荡组织的神经回路活动被破坏，并表明伽马振荡是AD患者认知功能障碍的可能机制之一。
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.