Enhanced Learning and Memory and Altered GABAergic Synaptic Transmission in Mice Lacking the α5 Subunit of the GABA_AReceptor

TLDR

The α5 subunit of the GABA_A receptor is localized mainly to the hippocampus of the mammalian brain. The significance of this distinct localization and the function of α5‑containing GABA_A receptors has been explored by targeted disruption of the α5 gene in mice. α5−/− mice exhibited enhanced spatial learning in a water maze, unchanged non‑hippocampal learning and anxiety, reduced CA1 IPSC amplitude, increased paired‑pulse facilitation, indicating that α5‑containing GABA_A receptors modulate hippocampal synaptic transmission and cognitive function.

Abstract

The α5 subunit of the GABA_A receptor is localized mainly to the hippocampus of the mammalian brain. The significance of this rather distinct localization and the function of α5-containing GABA_A 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 GABA_A receptors play a key role in cognitive processes by controlling a component of synaptic transmission in the CA1 region of the hippocampus.