General anesthetics can interfere with dendritic signal conduction in pyramidal neurons through at least four mechanisms. (A) Anesthetics can suppress the generation of dendritic calcium action potentials that carry signals along the main apical dendrite toward the soma. (B) They can suppress regenerative N-methyl-d-aspartate (NMDA) potentials that carry signals from peripheral tuft dendrites toward the calcium potential initiation zone. (C) Anesthetics can up-regulate inhibitory interneurons that, in turn, suppress the generation of dendritic calcium action potentials (see also fig. 5 and the accompanying legend). (D) Anesthetics can inhibit the hyperpolarization-activated current I_h, a leak conductance, which uncouples the somatic and dendritic compartments of the pyramidal cell under physiological conditions. When I_h is blocked, somatic activation alone may trigger a dendritic calcium spike and the subsequent burst of somatic action potentials, leading to a breakdown of the unique associative mechanism afforded by pyramidal cells between input to their somatic and dendritic compartments. GABA = γ-aminobutyric acid.