Sevoflurane-induced loss of consciousness is paralleled by a prominent modification of neural activity during cortical down-states

Abstract

Networks of neocortical neurons display a bistable activity pattern characterised by phases of high frequency action potential firing, so called up-states, and episodes of low discharge activity (down-states). We hypothesised that during down-states neocortical neurons are vulnerable to anaesthetic agents. To tackle this issue, it is necessary to identify analytical methods, which are sufficiently sensitive for resolving anaesthetic effects during phases of scarce neuronal activity. The local field potential was recorded in organotypic cultures (OTC) from rat neocortex under control conditions and in the presence of increasing concentrations of sevoflurane by extracellular electrodes. Epochs from down-states were cut from the local field potential and analysed using power spectrum density as well as non-linear parameters approximate entropy (ApEn) and order recurrence rate (ORR). ApEn and ORR proved to be suitable tools for analysing the actions of volatile anaesthetics on cortical down-states. During these phases of low neuronal activity, sevoflurane caused prominent changes in the local field potential. Time series analysis using ApEn showed a reduction of signal predictability in the presence of sevoflurane. Furthermore, the ORR displayed an abrupt decrease at sevoflurane concentrations corresponding to loss of consciousness in vivo, indicating a drug-induced decrease in the signal to noise ratio. The actions of volatile anaesthetics on cortical down-states have been neglected so far, perhaps due to the lack of suitable analysis tools. In the current in vitro study the non-linear parameters ApEn and ORR are introduced to characterise volatile anaesthetics actions. Sevoflurane alters cortical down-states as indicated by non-linear parameter analysis of local field potential recording from cultured neuronal networks. ORR even displays an abrupt change, i.e., a step-like behaviour indicating an increased signal complexity at concentrations of sevoflurane corresponding to loss of consciousness in humans.