The role of the NMDA synapse in general anesthesia

A theory of anesthesia is presented. It consists of four hypotheses. (1) The occurrence of states of consciousness causally depends on the formation of transient higher-order, self-referential mental representations. The occurrence of such states is identical with the appearance of conscious phenomena. Loss of consciousness will occur, if the brain's representational activity falls below a critical threshold. (2) Higher-order mental representations are instantiated by neural cell assemblies. (3) The formation of such assemblies involves the activation of the NMDA receptor channel complex. The activation state of this receptor determines the rate at which such assemblies are generated. (4) Modification of NMDA-dependent computational processes is the final common pathway of anesthetic action. Agents that directly inactivate the NMDA synapse necessarily have anesthetic properties; agents that do not directly affect the NMDA synapse will exert an anesthetic action, if they inhibit NMDA-dependent processes. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.