Energy and Potassium Ion Homeostasis during Gamma Oscillations

Fast neuronal network oscillations in the gamma frequency band (30-100 Hz) occur in various cortex regions, require timed synaptic excitation and inhibition with glutamate and GABA, respectively, and are associated with higher brain functions such as sensory perception, attentional selection and memory formation. However, little is known about energy and ion homeostasis during the gamma oscillation. Recent studies addressed this topic in slices of the rodent hippocampus using cholinergic and glutamatergic receptor models of gamma oscillations (GAM). Methods with high spatial and temporal resolution were applied in vitro, such as electrophysiological recordings of local field potential (LFP) and extracellular potassium concentration ([K(+)]o), live-cell fluorescence imaging of nicotinamide adenine dinucleotide (phosphate) and flavin adenine dinucleotide [NAD(P)H and FAD, respectively] (cellular redox state), and monitoring of the interstitial partial oxygen pressure (pO2) in depth profiles with microsensor electrodes, including mathematical modeling. The main findings are: (i) GAM are associated with high oxygen consumption rate and significant changes in the cellular redox state, indicating rapid adaptations in glycolysis and oxidative phosphorylation; (ii) GAM are accompanied by fluctuating elevations in [K(+)]o of less than 0.5 mmol/L from baseline, likely reflecting effective K(+)-uptake mechanisms of neuron and astrocyte compartments; and (iii) GAM are exquisitely sensitive to metabolic stress induced by lowering oxygen availability or by pharmacological inhibition of the mitochondrial respiratory chain. These findings reflect precise cellular adaptations to maintain adenosine-5'-triphosphate (ATP), ion and neurotransmitter homeostasis and thus neural excitability and synaptic signaling during GAM. Conversely, the exquisite sensitivity of GAM to metabolic stress might significantly contribute the exceptional vulnerability of higher brain functions in brain disease.