Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the α5 subunit of the GABAA receptor

Abstract

The α5 subunit of the GABAA receptor is localized mainly to the hippocampus of the mammalian brain. The significance of this rather distinct localization and the function of α5-containing GABAA receptors has been explored by targeted disruption of the α5 gene in mice. The α5 -/- mice showed a significantly improved performance in a water maze model of spatial learning, whereas the performance in non-hippocampal-dependent learning and in anxiety tasks were unaltered in comparison with wild-type controls. In the CA1 region of hippocampal brain slices from α5 -/- mice, the amplitude of the IPSCs was decreased, and paired-pulse facilitation of field EPSP (fEPSP) amplitudes was enhanced. These data suggest that α5-containing GABAA receptors play a key role in cognitive processes by controlling a component of synaptic transmission in the CA1 region of the hippocampus.