Institute for Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Brain. 2011 Feb;134(Pt 2):345-58. doi: 10.1093/brain/awq333. Epub 2010 Dec 22.
Fast neuronal network oscillations in the gamma range (~30-90 Hz) have been implicated in complex brain functions such as sensory processing, memory formation and, perhaps, consciousness, and appear to be exceptionally vulnerable to various pathologies. However, both energy demand and mitochondrial performance underlying gamma oscillations are unknown. We investigated the fundamental relationship between acetylcholine-induced gamma oscillations, mitochondrial gene expression and oxidative metabolism in hippocampal slice preparations of mouse and rat by applying electrophysiology, in situ hybridization, quantitative polymerase chain reaction, oxygen sensor microelectrode (interstitial partial oxygen pressure) and imaging of mitochondrial redox state [nicotinamide adenine dinucleotide (phosphate) and flavin adenine dinucleotide fluorescence]. We show that (i) gamma oscillation power, oxygen consumption and expression of complex I (nicotinamide adenine dinucleotide:ubiquinone oxidoreductase) subunits are higher in hippocampal subfield CA3 than in CA1 and dentate gyrus; (ii) the amount of oxygen consumption of gamma oscillations reaches that of seizure-like events; (iii) gamma oscillations are exquisitely sensitive to pharmacological complex I inhibition; and (iv) gamma oscillations utilize mitochondrial oxidative capacity near limit. These data suggest that gamma oscillations are especially energy demanding and require both high complex I expression and strong functional performance of mitochondria. Our study helps to explain the exceptional vulnerability of complex brain functions in ischaemia as well as in neurodegenerative and psychiatric disorders that are associated with mitochondrial dysfunction.
快速神经元网络在伽马频段（~30-90 Hz）的震荡与复杂的大脑功能有关，例如感觉处理、记忆形成，甚至可能与意识有关，并且似乎对各种病理状况特别敏感。然而，伽马震荡所需要的能量和线粒体的功能仍不清楚。我们通过应用电生理学、原位杂交、定量聚合酶链反应、氧传感器微电极（间质局部氧压）和线粒体氧化还原状态的成像[烟酰胺腺嘌呤二核苷酸（磷酸）和黄素腺嘌呤二核苷酸荧光]，研究了小鼠和大鼠海马切片中乙酰胆碱诱导的伽马震荡、线粒体基因表达和氧化代谢之间的基本关系。我们发现：（i）海马的 CA3 区比 CA1 区和齿状回区的伽马震荡功率、耗氧量和复合物 I（烟酰胺腺嘌呤二核苷酸：泛醌氧化还原酶）亚基的表达更高；（ii）伽马震荡的耗氧量达到类似癫痫发作事件的水平；（iii）伽马震荡对药理学上的复合物 I 抑制非常敏感；（iv）伽马震荡利用接近极限的线粒体氧化能力。这些数据表明，伽马震荡特别需要能量，需要高复合物 I 表达和线粒体的强大功能表现。我们的研究有助于解释与线粒体功能障碍有关的缺血以及神经退行性和精神障碍中复杂大脑功能的异常脆弱性。
