Patients with panic disorders show a deficit of GABA A receptors in the hippocampus, parahippocampus and orbitofrontal cortex. Synaptic clustering of GABA A receptors in mice heterozygous for the γ2 subunit was reduced, mainly in hippocampus and cerebral cortex. The γ2+/–mice showed enhanced behavioral inhibition toward natural aversive stimuli and heightened responsiveness in trace fear conditioning and ambiguous cue discrimination learning. Implicit and spatial memory as well as long-term potentiation in hippocampus were unchanged. Thus γ2+/–mice represent a model of anxiety characterized by harm avoidance behavior and an explicit memory bias for threat cues, resulting in heightened sensitivity to negative associations. This model implicates GABA A-receptor dysfunction in patients as a causal predisposition to anxiety disorders.