Abstractγ-aminobutyric acid type A receptors that incorporate α5 subunits (α5-GABAARs) are highly enriched in the hippocampus and they are strongly implicated in the control of learning and memory. Receptors located on pyramidal neuron dendrites have long been considered responsible, but here we report that selective elimination of α5-GABAARs from either interneurons or pyramidal cells prevented the general anesthetic etomidate from suppressing contextual learning. Using Ca2+ imaging of hippocampal neuronal activity in freely exploring mice, we also found that etomidate interfered with the development of place cells and spatial engrams in wild type mice but not in interneuron-specific α5-GABAAR knockout mice. These findings show that α5-GABAARs on interneurons as well as pyramidal neurons mediate etomidate-induced amnesia.