Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease
Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease
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DOI：
10.1126/science.1162844
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发表时间：
2008-09-19
期刊：
影响因子：
56.9
通讯作者：
Garaschuk, Olga
中科院分区：
文献类型：
--
作者：
Busche, Marc Aurel;Eichhoff, Gerhard;Garaschuk, Olga
在阿尔茨海默病中观察到的神经退行性变与突触拆除和神经元活性的进行性降低有关。我们在阿尔茨海默病小鼠模型中使用双光子Ca（2+）成像在体内验证了这一假设。尽管29%的2/3层皮质神经元活性下降，但21%的神经元显示自发Ca（2+）瞬态频率意外增加。这些“过度活跃”的神经元只在淀粉样蛋白沉积小鼠的斑块附近被发现。这种过度活跃似乎是由于突触抑制的相对减少。因此，我们认为突触驱动在沉默和过度活跃的神经元之间的重新分配，而不是突触活动的整体减少，提供了阿尔茨海默病皮层功能紊乱的机制。
The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two- photon Ca(2+) imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca(2+) transients. These "hyperactive" neurons were found exclusively near the plaques of amyloid beta-depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.