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Abstract

It has been proposed that cortical gamma rhythms are generated within networks of GABAergic interneurones (mutual inhibition; Whittington et al., Nature 373:612-615, 1995). To test this hypothesis, the actions of the volatile anaesthetic isoflurane on 40 Hz-oscillations in the human EEG were compared with those in neocortical brain slices. At 0.15-0.2 mM, isoflurane induced the loss of consciousness in man and simultaneously decreased the frequency of auditory evoked gamma-oscillations in the EEG by 50 per cent (Madler et al. 1991, Br.J.Anaesth.). The mutual inhibition model predicts that changes in the frequency of gamma oscillations should be inversely related to changes in the decay time constant of GABAA-receptor mediated synaptic currents (IPSCs). To test this prediction, we determined the effects of isoflurane on IPSCs recorded from voltage-clamped pyramidal cells and on gamma oscillations, detected in the local field potential of brain slices. The results were indeed in good accordance with the model: At 0.16 mM, isoflurane lengthened IPSC-decays by a factor of 1.7 and decreased the frequency of gamma oscillations by 41 per cent. NMDA-receptor antagonists like ketamine are also potent general anaesthetics but leave sensory evoked gamma-oscillations unaffected. In vivo studies have shown that, in the primary somatosensory and visual cortex, NMDA-receptor-antagonists do not alter stimulus evoked firing in cortical layers 4-6 but abolish the responses of layer 2 cells. This may indicate that, in contrast to recent suggestions (Gray/McCormick, Science 274: 109-113, 1996), pyramidal cells in the superficial layers are not an essential part of the oscillator mechanism.