Constitutive Girk2 −/− mice exhibit an array of neurological phenotypes, including impaired fear learning6, 61. The global nature of the genetic manipulation, however, complicates attempts to link the phenotype to a defined neuron population. Accordingly, we developed conditional Girk2 −/− (Girk2 fl/fl) mice and have crossed them with transgenic Cre driver lines to permit GIRK channel ablation in a neuron-specific manner6, 61. In CaMKIICre(+):Girk2 fl/fl mice, Girk2 ablation is driven by Cre recombinase, expressed under the control of the CaMKIIα promoter. While the CaMKIICre driver line is generally considered to promote gene ablation in postnatal forebrain pyramidal neurons, the scope of recombination achieved with this driver line depends on the “floxed” gene in question, with some studies showing highly restricted target loss in dorsal CA1 pyramidal neurons and others showing recombination in multiple forebrain pyramidal neuron populations62–67. We found that GIRK2 expression was preserved in most forebrain structures in CaMKIICre(+):Girk2 fl/fl mice, but that GIRK-dependent signaling was blunted in dorsal (but not ventral) CA1 pyramidal neurons6.
