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.
Highlights
General anesthesia is used daily to enable surgery, but its underlying mechanisms of action are still largely a mystery
With the help of this model, we demonstrate the role of extra-synaptic GABAergic inhibition, and the importance of tonic inhibition in the cortical inhibitory neuronal population, in explaining experimental electroencephalographic data (EEG) power spectra
To understand how propofol might enhance δ− and α−power, we study the power spectrum of our theoretical model for different anesthetic concentration levels and examine the impact of adding tonic inhibition via extra-synaptic GABAA receptors
Summary
General anesthesia is used daily to enable surgery, but its underlying mechanisms of action are still largely a mystery. Several previous theoretical studies have proposed neural models to explain certain EEG signal features observed during anesthesia (Steyn-Ross et al, 1999, 2013; Bojak and Liley, 2005; Wilson et al, 2006; Foster et al, 2008; McCarthy et al, 2008; Ching et al, 2010, 2012; Hutt, 2013; Liley and Walsh, 2013; Hutt et al, 2013; Hutt and Buhry, 2014) These studies may incorporate realistic neurobiological details of the brains’ network topology and neuronal function, they have simplified dramatically the anesthetic action by considering only synaptic excitatory and inhibitory receptors. There is a growing amount of experimental research that has revealed the importance of extra-synaptic receptors (ESR) for neural interactions in general (Brickley and Mody, 2012; Hardingham and Bading, 2012), and for anesthesia especially, see Alkire et al (2008); Hutt (2012) and references therein
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