Tonic inhibition mediates a synchronisation enhancement during propofol anaesthesia in a network of hippocampal interneurons: a modelling study
Résumé
Neural oscillations are thought to be correlated with the execution of cognitive functions. Indeed, gamma oscillations are often recorded in functionally-coupled brain regions for cooperation during memory tasks, and this rhythmic behaviour is thought to result from synaptic GABAergic interactions between in-terneurons. Interestingly, GABAergic synaptic and ex-trasynaptic receptors have been shown to be the preferred target of the most commonly used anaesthetic agents. We present a in-depth computational study of the action of anaesthesia on neural oscillations by introducing a new mathematical model which takes into account the four main effects of the anaesthetic agent propofol on GABAergic hippocampal interneurons. These are: the action on synaptic GABA A receptors, which includes an amplification and an extension of the duration of the synaptic currents, as well as an increase in current baseline, and the action on extrasynaptic GABA A receptors mediating a tonic inhibitory current. Our results indicate that propofol-mediated tonic inhibition contributes to an unexpected enhancement of synchro-nisation in the activity of a network of hippocampal interneurons. We speculate that this enhanced synchro-nisation could provide a possible mechanism supporting the occurrence of intraoperative awareness and explicit memory formationunder general anaesthesia, by transiently facilitating the communication between brain structures which should supposedly be not allowed to do so when anaesthetised.
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