Inhibitory neuron and hippocampal circuit dysfunction in an aged mouse model of Alzheimer's disease.
Inhibitory neuron and hippocampal circuit dysfunction in an aged mouse model of Alzheimer's disease.
复制标题
DOI：
10.1371/journal.pone.0064318
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ziburkus J
中科院分区：
文献类型：
--
作者：
Hazra A;Gu F;Aulakh A;Berridge C;Eriksen JL;Ziburkus J
在阿尔茨海默病（AD）中，外显记忆下降是疾病的最早迹象之一，并与海马功能障碍有关。淀粉样蛋白对神经元功能产生破坏性影响，但对海马网络活动的具体影响尚不清楚。在这项研究中，快速电压敏感染料成像和细胞外和全细胞电生理学用于内嗅皮质-海马切片制备，以表征12-16个月大的雌性APPswe/PSEN 1DeltaE 9（APdE 9小鼠）小鼠的海马网络活动。老年APdE 9小鼠在齿状回回路激活中表现出严重的中断。在APdE 9小鼠组织的齿状回（DG）区域中的穿通通路的高频刺激诱发了与更宽的神经激活图相对应的异常大的场电位响应。全细胞膜片钳记录DG分子层中识别的抑制性中间神经元显示，它们不能可靠地激发动作电位。两者合计，异常DG兴奋性和抑制性神经元产生动作电位的失败被认为是早期阿尔茨海默病病理生理学的潜在细胞机制的重要贡献者。
In Alzheimer's disease (AD), a decline in explicit memory is one of the earliest signs of disease and is associated with hippocampal dysfunction. Amyloid protein exerts a disruptive impact on neuronal function, but the specific effects on hippocampal network activity are not well known. In this study, fast voltage-sensitive dye imaging and extracellular and whole-cell electrophysiology were used on entorhinal cortical-hippocampal slice preparations to characterize hippocampal network activity in 12–16 month old female APPswe/PSEN1DeltaE9 (APdE9 mice) mice. Aged APdE9 mice exhibited profound disruptions in dentate gyrus circuit activation. High frequency stimulation of the perforant pathway in the dentate gyrus (DG) area of APdE9 mouse tissue evoked abnormally large field potential responses corresponding to the wider neural activation maps. Whole-cell patch clamp recordings of the identified inhibitory interneurons in the molecular layer of DG revealed that they fail to reliably fire action potentials. Taken together, abnormal DG excitability and an inhibitory neuron failure to generate action potentials are suggested to be important contributors to the underlying cellular mechanisms of early-stage Alzheimer's disease pathophysiology.
登录
查看更多内容
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
14.8
作者：
Carlson, Greg C.;Coulter, Douglas A.
通讯作者：
Coulter, Douglas A.
影响因子：
2.2
作者：
Cloyd, J;Hauser, W;Walczak, T
通讯作者：
Walczak, T
影响因子：
25
作者：
Cleary, JP;Walsh, DM;Ashe, KH
通讯作者：
Ashe, KH
影响因子：
3.2
作者：
Culmone, Viviana;Migliore, Michele
通讯作者：
Migliore, Michele