The NMDA receptor and general anaesthetic action

Hans Flohr
Brain Research Institute, University of Bremen, Germany

A hypothesis is developed that the NMDA receptors of glutamatergic cortical synapses play a crucial role in both the generation of conscious states and as the ultimate targets for anaesthetic action (Flohr 1991, 1995):

1. The occurence of states of consciousness causally depends on the formation of higher-order mental representations;

2. higher-order mental representations are realized by large-scale neuronal assemblies;

3. the formation of such assemblies is made possible by the cortical NMDA synapse. This synapse implements the binding mechanism that the brain uses to produce large-scale neuronal assemblies;

4. an inhibition of these NMDA-dependent binding processses is the final common pathway of general anaesthetic action.

Current experimental evidence supports this hypothesis. All agents that directly inhibit the activation of the NMDA receptor or the subsequent plastic processes triggered by Ca²⁺ possess anaesthetic properties. The anaesthetic action of agents that primarily interact with other targets can be explained as an indirect effect on the NMDA synapse.

Flohr, H. (1991) Theory and Psychology 1, 245-262

Flohr, H. (1995) Neuropsychologia 33, 1169-1180