Home > Conscious > Chapter 7 > 7.8. General Anesthetics


Most general anesthetics cause unconsciousness by potentiating GABAA receptors (Alkire et al., 2008). According to the Alpha Hypothesis, consciousness arises from globally synchronized α oscillations. Potentiation of the GABAA receptors may inhibit the release of wake-promoting neurotransmitters (see Figure 7-7), thereby suppressing the α activities. Furthermore, a great majority of general anesthetics increase slow oscillations (Steriade et al., 1993; Nelson et al., 2010; Sarasso et al., 2015; Pavone et al., 2016), which could be the major cause of unconsciousness.

Slow oscillations are local activities. They disrupt global synchronization, resulting in fragmentation of neuronal networks (Lewis et al., 2012). As discussed in Section 7.6, slow oscillations could be facilitated by pyramidal neurons containing HCN channels. The general anesthetics in Figure 7-10 have been demonstrated to inhibit HCN channels (Zhou et al., 2012; Chen et al., 2005; Chen et al., 2009a; Chen et al., 2009b; Mattusch et al., 2015). All of them also increase slow oscillations.


Figure 7-10. The general anesthetics that have been shown to inhibit HCN channels and increase slow oscillations.

Ketamine does not interact with GABAA receptors. Together with nitrous oxide and xenon, they block NMDA receptors (Alkire et al., 2008). Ketamine increases the cerebral blood flow and/or glucose metabolic rate in the thalamus and anterior cingulate cortex, suggesting that neuronal activities are enhanced at the two regions that generate α rhythms (Langsjo et al., 2005). Further studies demonstrate that ketamine increases both gamma and theta oscillations, but reduces the α rhythms (Muthukumaraswam et al., 2015; Akeju et al., 2016). The frontal-parietal connectivity in the alpha band is also reduced by ketamine (Blain-Moraes et al., 2014).

Hence, both natural sleep and general anesthesia support the Alpha Hypothesis that consciousness arises from globally synchronized α oscillations. The next two chapters will explore consciousness at a more fundamental level.