Gamma oscillations and spontaneous network activity in the hippocampus are highly sensitive to decreases in pO2 and concomitant changes in mitochondrial redox state
Gamma oscillations and spontaneous network activity in the hippocampus are highly sensitive to decreases in pO2 and concomitant changes in mitochondrial redox state
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DOI：
10.1523/jneurosci.4105-07.2008
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发表时间：
2008-01-30
影响因子：
5.3
通讯作者：
Kann, Oliver
中科院分区：
文献类型：
--
作者：
Huchzermeyer, Christine;Albus, Klaus;Kann, Oliver
伽马振荡与高级认知过程有关，可能严重依赖于适当的线粒体功能。利用电生理学、氧传感器微电极和成像技术，我们研究了器官型海马脑片培养物CA3区神经元活动、间质pO（2）和线粒体氧化还原状态[NAD（P）H和FAD（黄素腺嘌呤二核苷酸）荧光]的相互作用。我们发现，γ振荡和自发网络活动显着降低pO（2）水平，不影响神经元群体的反应，引起适度的电刺激。此外，pO（2）和线粒体氧化还原状态是紧密耦合的，当pO（2）在正常含氧量范围内降低时，电刺激揭示了氧化还原反应的瞬时变化。最后，诱发的氧化还原反应在体细胞和突触神经元隔室中是不同的，并且对pO（2）的变化表现出不同的敏感性。我们的结论是，对于强大的CA3网络活动和所需的线粒体功能，间质pO（2）的阈值明显高于“临界”值，这会导致广泛的能量衰竭导致扩散性抑郁。我们的研究强调了线粒体功能理解的重要性及其对单个神经元和神经元网络活动的影响。
Gamma oscillations have been implicated in higher cognitive processes and might critically depend on proper mitochondrial function. Using electrophysiology, oxygen sensor microelectrode, and imaging techniques, we investigated the interactions of neuronal activity, interstitial pO(2), and mitochondrial redox state [NAD(P) H and FAD (flavin adenine dinucleotide) fluorescence] in the CA3 subfield of organotypic hippocampal slice cultures. We find that gamma oscillations and spontaneous network activity decrease significantly at pO(2) levels that do not affect neuronal population responses as elicited by moderate electrical stimuli. Moreover, pO(2) and mitochondrial redox states are tightly coupled, and electrical stimuli reveal transient alterations of redox responses when pO(2) decreases within the normoxic range. Finally, evoked redox responses are distinct in somatic and synaptic neuronal compartments and show different sensitivity to changes in pO(2). We conclude that the threshold of interstitial pO(2) for robust CA3 network activities and required mitochondrial function is clearly above the " critical" value, which causes spreading depression as a result of generalized energy failure. Our study highlights the importance of a functional understanding of mitochondria and their implications on activities of individual neurons and neuronal networks.