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BACKGROUND: General anaesthesia is known to enhance inhibitory synaptic transmission to produce characteristic effects on the EEG and reduction in brain metabolism secondary to reduced neuronal activity. Evidence suggests that anaesthesia might have a direct effect on synaptic metabolic processes, and this relates to anaesthesia sensitivity. We explored elements of synaptic transmission looking for possible contributions to the anaesthetised EEG and how it may modulate anaesthesia sensitivity. METHODS: We developed a Hodgkin-Huxley-type neural network computer simulation capable of mimicking anaesthetic prolongation of gamma-aminobutyric acid (GABA)ergic inhibitory postsynaptic potentials (IPSPs), and capable of altering postsynaptic ion homeostasis and neurotransmitter recycling. We examined their interactions on simulated electrocorticography (sECoG), and compared these with published anaesthesia EEG spectra. RESULTS: The sECoG spectra from the model were comparable with published normal awake EEG spectra. Prolongation of IPSP duration in the model caused inhibition of high frequencies and saturation of low frequencies with a peak in keeping with current evidence. IPSP prolongation alone was unable to reproduce alpha rhythms or the generalised increase in EEG power found with anaesthesia. Adding inhibition of postsynaptic ion homeostasis to IPSP prolongation helped retain alpha rhythms, increased sECoG power, and antagonised the slow-wave saturation peak in a dose-dependent fashion that appeared dependent on the postsynaptic membrane potential, providing a plausible mechanism for how metabolic changes can modulate anaesthesia sensitivity. CONCLUSIONS: Our model suggests how metabolic processes can modulate anaesthesia and produce non-receptor dependent drug sensitivity.

Original publication

DOI

10.1016/j.bja.2021.01.034

Type

Journal article

Journal

Br J Anaesth

Publication Date

05/2021

Volume

126

Pages

985 - 995

Keywords

anaesthesia, computer modelling, electrocorticogram, electroencephalogram, ion gradients, metabolism, synapse, Anesthesia, General, Anesthetics, General, Astrocytes, Computer Simulation, Dose-Response Relationship, Drug, Electrocorticography, Electroencephalography, Neural Networks, Computer, Synaptic Transmission, gamma-Aminobutyric Acid