Propofol-induced GABAergic Tonic Inhibition Diminishes -rhythms and Induces -rhythms in neuronal populations

Anaesthetic agents such as propofol are known to have an effect on both synaptic and extra-synaptic receptors. On the one hand, binding of propofol to GABA A synaptic receptors induces a phasic inhibition, as opposed to tonic inhibition which seems mainly induced by binding to extra-synaptic receptors. On the second hand, under aneasthesia, an increase in amount of slow oscillations, mainly δ (0-4Hz), concurrent to a decrease of α oscillations (8-12Hz), is observed in EEG recordings of occipital areas in most mammals including humans. The latter observation cannot be explained by sole phasic inhibition. Therefore, we propose to investigate, through numerical simulations, the role of tonic inhibition in the increase (in amount) of slow oscillations under propofol anaesthesia. To account for the biological realism of our simulations, the cortical model includes two neuronal populations, one excitatory modeled by Type I Leaky integrate-and-fire neurons, one inhibitory modeled by Type II Morris-Lecar neurons, the stimulations are noisy, and the intrinsic cellular properties heterogeneous. The cells are connected through exponential conductance-based synapses. We show that, in presence of tonic inhibition, 1) the oscillation frequency of the network decreases as well as subthreshold oscillations, inducing δ-rhythms in EEG-like recordings; 2) simulatneously, the amount of α-rhythms decreases supporting experimental evidence about the role of tonic inhibition. Preprint submitted to RR-8230 February 11, 2013 ha l-0 07 87 31 7, v er si on 1 11 F eb 2 01 3