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Abstract:
It has been proposed that cortical gamma rhythms are generated withinnetworks of GABAergic interneurones (mutual inhibition; Whittington etal., Nature 373:612-615, 1995). To test this hypothesis, the actions ofthe volatile anaesthetic isoflurane on 40 Hz-oscillations in the humanEEG were compared with those in neocortical brain slices. At 0.15-0.2mM, isoflurane induced the loss of consciousness in man andsimultaneously 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 thefrequency of gamma oscillations should be inversely related to changesin the decay time constant of GABAA-receptor mediated synapticcurrents (IPSCs). To test this prediction, we determined the effects ofisoflurane on IPSCs recorded from voltage-clamped pyramidal cells andon gamma oscillations, detected in the local field potential of brainslices. The results were indeed in good accordance with the model: At0.16 mM, isoflurane lengthened IPSC-decays by a factor of 1.7 anddecreased the frequency of gamma oscillations by 41 per cent. NMDA-receptor antagonists like ketamine are also potent general anaestheticsbut leave sensory evoked gamma-oscillations unaffected. In vivostudies have shown that, in the primary somatosensory and visualcortex, NMDA-receptor-antagonists do not alter stimulus evoked firingin cortical layers 4-6 but abolish the responses of layer 2 cells. Thismay indicate that, in contrast to recent suggestions (Gray/McCormick,Science 274: 109-113, 1996), pyramidal cells in the superficial layersare not an essential part of the oscillator mechanism.
