Specific roles of GABAB(1) receptor isoforms in cognition

The GABAB receptor is a heterodimer of GABAB(1) and GABAB(2) subunits. There are two isoforms of the GABAB(1) subunit: GABAB(1a) and GABAB(1b). Recent studies with mutant mice suggest a differential role for the two GABAB(1) isoforms in behavioural processes. As pharmacological and genetic studies have implicated GABAB receptors in cognition we investigated the behaviour of GABAB(1a)−/− and GABAB(1b)−/− mice in different types of cognitive paradigms. GABAB(1a)−/− and GABAB(1b)−/− mice were both impaired relative to wildtype controls in a continuous spontaneous alternation behaviour test of working spatial memory. In contrast to the reported phenotype of GABAB(1)−/− mice, however, neither GABAB(1a)−/− nor GABAB(1b)−/− mice were deficient in a passive avoidance task. On the other hand, GABAB(1a)−/− mice were impaired in familiar and novel object recognition. We conclude that GABAB(1) isoforms contribute differentially to GABAB receptor-mediated cognitive processes.