Specific roles of GABA(B(1)) receptor isoforms in cognition

Behav Brain Res. 2007 Jul 19;181(1):158-62. doi: 10.1016/j.bbr.2007.03.033. Epub 2007 Apr 5.

Abstract

The GABA(B) receptor is a heterodimer of GABA(B(1)) and GABA(B(2)) subunits. There are two isoforms of the GABA(B(1)) subunit: GABA(B(1a)) and GABA(B(1b)). Recent studies with mutant mice suggest a differential role for the two GABA(B(1)) isoforms in behavioural processes. As pharmacological and genetic studies have implicated GABA(B) receptors in cognition we investigated the behaviour of GABA(B(1a))(-/-) and GABA(B(1b))(-/-) mice in different types of cognitive paradigms. GABA(B(1a))(-/-) and GABA(B(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 GABA(B(1))(-/-) mice, however, neither GABA(B(1a))(-/-) nor GABA(B(1b))(-/-) mice were deficient in a passive avoidance task. On the other hand, GABA(B(1a))(-/-) mice were impaired in familiar and novel object recognition. We conclude that GABA(B(1)) isoforms contribute differentially to GABA(B) receptor-mediated cognitive processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Avoidance Learning / physiology
  • Behavior, Animal / physiology
  • Cognition / physiology*
  • Exploratory Behavior / physiology
  • Male
  • Maze Learning / physiology
  • Memory / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Protein Isoforms / deficiency
  • Protein Isoforms / physiology
  • Reaction Time / genetics
  • Receptors, GABA-B / deficiency
  • Receptors, GABA-B / physiology*

Substances

  • Protein Isoforms
  • Receptors, GABA-B