Tonic inhibition induces a decrease in the frequency bands of neuronal population activity: a modeling study for anesthetic effects
Résumé
Anaesthetic agents such as propofol are known to have an effect on GABA_A extrasynaptic receptors, inducing a tonic inhibition (Orser, J. Clin. Sleep Med., 2006) concurrently to phasic (synaptic) inhibition. However the relation of anesthetic action and tonic inhibition is still not well-known. Tonic inhibition seems to equally affect inhibitory and excitatory neurons (Song et al, Nature, 2011). It often has a shunting effect which arises when the (extra-)synaptic reversal potential is equal to the membrane resting potential of the neuron. At the behavioral level, when subjects are awake and close their eyes, we find a strong alpha component (8-12 Hz) in electroencephalograms (EEG). During general anaesthesia, the amount of alpha oscillations decreases and more delta oscillations (1-4 Hz) appear. The mechanisms that induce this decrease in oscillation frequency remains unknown. It is especially unclear whether this power decrease is due to interactions with the thalamus or whether tonic inhibition can induce, by itself, a decrease of frequency band in any neural population. To test the latter hypothesis, we simulate the activity of two connected neuronal populations, one excitatory and one inhibitory, with sparse connections. To make the model biologically plausible, the excitatory cells are modeled by Type I leaky- integrate-and-fire neurons (LIF) (Mitchell and Silver, Neuron, 2003) and inhibitory cells by Type II Morris-Lecar neurons (Borisyuk and Rinzel, Models and Meth. in Neurophysics, 2005); the neurons receive noisy external current-based inputs; and we add a conductance-based tonic inhibition to all neurons. In addition, the populations under study are heterogeneous involving distributions of firing thresholds and inhibitory conductances. We then record the membrane potential of all neurons while varying the amount of tonic inhibition, i.e. anesthetic concentration. We observe that, the more we increase the amplitude of tonic inhibition, the more delta frequencies appear in the power spectrum of the mean population membrane potential. This could suggest that tonic inhibition itself is able to induce the slow oscillation frequencies observed in EEG during general anaesthesia.