Anesthetic action on extra-synaptic receptors: effects in neural population models of EEG activity

Abstract

The role of extra-synaptic receptors in the regulation of excitation and inhibition in the brain has attracted increasing attention. Because activity in the extra-synaptic receptors plays a role in regulating the level of excitation and inhibition in the brain, they may be important in determining the level of consciousness. This paper reviews briefly the literature on extra-synaptic GABA and NMDA receptors and their affinity to anesthetic drugs. We propose a neural population model that illustrates how the effect of the anesthetic drug propofol on GABAergic extra-synaptic receptors results in changes in neural population activity and the electroencephalogram (EEG). Our results show that increased tonic inhibition in inhibitory cortical neurons cause a dramatic increase in the power of both δ− and α− bands. Conversely, the effects of increased tonic inhibition in cortical excitatory neurons and thalamic relay neurons have the opposite effect and decrease the power in these bands. The increased δ-activity is in accord with observed data for deepening propofol anesthesia; but is absolutely dependent on the inclusion of extrasynaptic (tonic) GABA action in the model.

How the cortico-thalamic feedback affects the EEG power spectrum over frontal and occipital regions during propofol-induced sedation

“…13) reveals that the δ−power surge is initiated at values p > 1, i.e., does not occur in the control condition (p = 1) but for increased anaesthetic concentration only. Hence, the spectral power peak in the δ−frequency band originates from the propofol-induced inhibition (Hashemi et al 2014).…”

“…This choice determines the maximum of thalamic response function to h max T = a i (α, β 0 i )A r (p), i.e., the maximum response increases with A r (p) under the condition A r (1) = 1. This choice is motivated by previous studies of cortical GABAergic synapses (Hashemi et al 2014;Hindriks and van Putten 2012). An optimal fit of A r to experimental data yields A r (p) ≈ 1.55 ln(1.49 + 0.42 exp(p)) ≈ p 0.42 , cf.…”

“…Other theoretical studies have pointed out the importance of anaesthetic-induced cortical inhibition considering (Hashemi et al 2014;Hindriks and van Putten 2012) or neglecting Bojak and Liley 2005;Steyn-Ross et al 1999;Steyn-Ross et al 2001a, b;Molaee-Ardekani et al 2007;Hutt and Longtin 2009) the feedback loop to the thalamus.…”

“…A large number of previous theoretical studies on anaesthetic effects apply a mean-field model to explain various features in EEG data recorded during general anaesthesia Bojak and Liley 2005;Steyn-Ross et al 1999;Steyn-Ross et al 2001a, b;Molaee-Ardekani et al 2007;Foster et al 2008;Hindriks and van Putten 2012;Hutt and Longtin 2009;Hashemi et al 2014). These theoretical studies are based on various extensions of the model of Liley and Wright (1994), Wright and Liley (1996), Wilson and Cowan (1972), and Amari (1977) including excitatory and inhibitory neurons and synapses.…”

“…The model takes into account anaesthetic action at inhibitory GABAergic synaptic receptors in both cortical inhibitory neurons and thalamic relay cells. A very recent model (Hashemi et al 2014) takes into account anaesthetic action of extra-synaptic GABAergic receptors, which are however neglected here.…”