Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 5, Pages 1153-1162Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4105-07.2008
Keywords
gamma; local field potential; mitochondria; NADPH; potassium concentration; [K]; tissue oxygen
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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.
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