Fast neuronal network oscillations in the gamma range (30–80 Hz) have been implicated in complex brain functions such as memory formation and might critically depend on sufficient ATP supply. Using electrophysiology, oxygen sensor microelectrodes and imaging techniques, we investigated the interactions of neuronal activity, interstitial pO₂ and mitochondrial redox state NAD(P)H and FAD fluorescence) in the CA3 subfield of organotypic hippocampal slice cultures.

Our findings are: 1) Gamma oscillations and spontaneous network activity decrease significantly at pO₂ levels that do not affect neuronal population responses as elicited by electrical stimuli. 2) pO₂ and mitochondrial redox state are tightly coupled. 3) Electrical stimuli reveal transient alterations of redox responses when the pO₂ decreases within the normoxic range. 4) Evoked redox responses are distinct in somatic and synaptic neuronal compartments and show different sensitivity to changes in pO₂. 5) Gamma oscillations are associated with high oxygen consumption. We conclude that gamma oscillations are highly energy consuming and critically depend on proper mitochondrial function.