Busche Marc Aurel, Eichhoff Gerhard, Adelsberger Helmuth, Abramowski Dorothee, Wiederhold Karl-Heinz, Haass Christian, Staufenbiel Matthias, Konnerth Arthur, Garaschuk Olga
Institut für Neurowissenschaften, Technische Universität München (TUM), 80802 München, Germany.
Science. 2008 Sep 19;321(5896):1686-9. doi: 10.1126/science.1162844.
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 Ca2+ 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 Ca2+ 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.
在阿尔茨海默病中观察到的神经退行性变与突触拆解和神经元活动的逐渐减少有关。我们通过在阿尔茨海默病小鼠模型中使用双光子Ca2+成像在体内验证了这一假设。尽管在29%的2/3层皮质神经元中观察到神经元活动减少，但21%的神经元显示出自发性Ca2+瞬变频率意外增加。这些“活跃过度”的神经元仅在淀粉样β沉积小鼠的斑块附近被发现。这种活跃过度似乎是由于突触抑制的相对减少所致。因此，我们认为沉默神经元和活跃过度神经元之间突触驱动的重新分配，而非突触活动的整体减少，为阿尔茨海默病中皮质功能紊乱提供了一种机制。
