Hippocampal α5 subunit-containing GABAA receptors are involved in the development of the latent inhibition effect

Hippocampal GABAA receptors containing the α5 subunit have been implicated in the modulation of hippocampal-dependent learning, presumably via their tonic inhibitory influence on hippocampal glutamatergic activity. Here, we examined the expression of latent inhibition (LI)—a form of selective learning that is sensitive to a number of manipulations targeted at the hippocampal formation, in α5(H105R) mutant mice with reduced levels of hippocampal α5-containing GABAA receptors. A single pre-exposure to the taste conditioned stimulus (CS) prior to the pairing of the same CS with LiCl-induced nausea was effective in reducing the conditioned aversion against the taste CS in wild-type mice—thus constituting the LI effect. LI was however distinctly absent in male α5(H105R) mutant mice. Hence, a partial loss of hippocampal α5 GABAA receptors is sufficient to alter one major form of selective learning, albeit this was not seen in the female. This observed phenotype suggests that specific activation of these extrasynaptic GABAA receptors may confer therapeutic potential against the failure to show selectivity in learning by human psychotic patients.