The lack of natural connectivity and normal afferent inputs to cultured neurons complicates efforts to study the full range of physiological contributions made by GIRK channels to pyramidal neuron excitability. Thus, we next examined the functional properties of GIRK2a and GIRK2c in organotypic hippocampal slices. Organotypic hippocampal slices were cultured from young wild-type or Girk2 −/− mice (P8–9), and the CA1 region was targeted with control or GIRK2 isoform-specific expression viruses (Fig. 6A). Following a 1-wk incubation period, we measured somatodendritic and synaptic GIRK-dependent responses in infected dorsal CA1 pyramidal neurons. Consistent with our observations in infected Girk2 −/− pyramidal neurons in culture, we observed larger baclofen-induced somatodendritic currents in dorsal Girk2 −/− CA1 pyramidal neurons expressing either GIRK2a or GIRK2c, as compared to wild-type controls (Fig. 6B ).
