Mechanisms of anesthesia: Towards integrating network, cellular, and molecular level modeling

Abstract

The mechanisms of anesthesia are surprisingly little understood. The present article summarizes current knowledge about the function of generalanesthetics at different organization levels of the nervous system. It argues that a consensus view can be constructed, assuming that generalanesthetics modulate the activity of ion channels, the main targets being GABA and NMDA channels and possibly voltagegated and background channels, thereby hyperpolarizing neurons in thalamocorticalloops, which lead to disruption of coherent oscillatory activity in the cortex. Two computationalcases are used to illustrate the possible importance of molecular leveleffects on cellular levelactivity. Subtle differences in the mechanism of ion channel block can be shown to cause considerable differences in the modification of the oscillatory activity in a single neuron, and consequently in an associated network. Finally, the relation between the anesthesia problem and the classical consciousness problem is discussed, and some consequences of introducing the phenomenon of degeneracy into the picture are pointed out. © 2003 Nature Publishing Group.