α2 GABA_A receptor sub-units in the ventral hippocampus and α5 GABA_A receptor sub-units in the dorsal hippocampus mediate anxiety and fear memory

Temporary neuronal inactivation of the ventral hippocampus with the GABA_A agonist muscimol suppresses unconditioned fear behavior (anxiety) but inactivation of the dorsal hippocampus does not. On the other hand, inactivating the dorsal hippocampus disrupts fear memory, while inactivating the ventral hippocampus does not. Here we investigate the roles of hippocampal GABA_A receptor sub-units in mediating these anxiolytic and amnesic effects of GABA_A receptor agonists. We microinfused TPA023 (α2 agonist) or TB-21007 (inverse α5 agonist) into the dorsal or ventral hippocampus prior to testing rats in two animal models of anxiety: the elevated plus-maze and shock-probe burying test. Twenty-four hours later rats were re-tested in the shock-probe chamber with a non-electrified probe to assess their memory of the initial shock-probe experience (i.e., fear memory). We found that TPA023 was anxiolytic in the plus-maze and shock-probe burying tests when microinfused into the ventral hippocampus. However, TPA023 did not affect anxiety-related behavior when infused into the dorsal hippocampus. Conversely, we found that the α5 sub-unit inverse agonist TB-21007 impaired rats' memory of the initial shock-probe experience when infused into the dorsal hippocampus, but not when infused into the ventral hippocampus. This double dissociation suggests that α2 GABA_A receptor sub-units in the ventral hippocampus mediate unconditioned fear or anxiety, while α5 GABA_A receptor sub-units in the dorsal hippocampus mediate conditioned fear memory.