Strain-dependent hippocampal protein levels of GABA(B)-receptor subunit 2 and NMDA-receptor subunit 1

Mouse strains differ from one another in cognitive function as learning and memory as well as synaptic plasticity. Although molecular explanations for this heterogeneity have been proposed, there is no available information on strain-dependent GABA(B)-receptor levels in hippocampus that may explain observed differences in GABA(B)-receptor-mediated cognitive enhancement among strains. This formed the rationale to perform a study on GABA(B) and related somatostatin receptor 5 and NMDA receptors that have been reported to be involved in memory enhancement by GABA(B)-antagonism. Hippocampi of three inbred (C57BL/6J, DBA/2, BalbC) and three outbred (OF1, CD1, CF1) mouse strains were taken. Membrane fractions were prepared and subsequently levels of GABA(B)-receptor subunits 1 and 2, NMDA-receptor subunits 1 and 2a and b, as well as somatostatin receptor 5 were determined by immunoblotting. NMDA-receptor subunit 1 levels were significantly higher in C57BL/6J than in DBA/2. GABA(B)-receptor subunit 2 levels were significantly decreased in C57BL/6J as compared to OF1, CD1, CF1 and DBA/2. No statistically significant differences for other receptors were observed. Different NMDA-receptor subunit 1 and GABA(B)-receptor subunit 2 levels observed in naive mouse strains reflect strain-dependent expression of subunits and are proposed to lead to altered stoichiometry of GABA(B)-receptor complexes. Modification of receptor complex stoichiometry in the hippocampus in turn may well be responsible for cognitive differences observed in spatial memory between mouse strains.