Relevance of Cortical and Hippocampal Interneuron Functional Diversity to General Anesthetic Mechanisms: A Narrative Review

Abstract

General anesthetics disrupt brain processes involved in consciousness by altering synaptic patterns of excitation and inhibition. In the cerebral cortex and hippocampus, GABAergic inhibition is largely mediated by inhibitory interneurons, a heterogeneous group of specialized neuronal subtypes that form characteristic microcircuits with excitatory neurons. Distinct interneuron subtypes regulate specific excitatory neuron networks during normal behavior, but how these interneuron subtypes are affected by general anesthetics is unclear. This narrative review summarizes current principles of the synaptic architecture of cortical and interneuron subtypes, their contributions to different forms of inhibition, and their roles in distinct neuronal microcircuits. The molecular and cellular targets in these circuits that are sensitive to anesthetics are reviewed in the context of how anesthetics impact interneuron function in a subtype-specific manner. The implications of this functional interneuron diversity for mechanisms of anesthesia are discussed, as are their implications for anesthetic-induced changes in neural plasticity and overall brain function.