HIPPOCAMPAL CELL RESPONSES IN MICE WITH A TARGETED GLUCOCORTICOID RECEPTOR GENE DISRUPTION

Previous studies in rats have shown that cellular properties of hippoc ampal CA1 neurons are under coordinative control of mineralocorticoid and glucocorticoid receptors (MRs and GRs, respectively). In the prese nt study, we examined electrical properties under conditions of exclus ive MR occupation, by using mice with a genetic defect in GRs obtained by homologous recombination techniques. It appeared that in the anima ls homozygous for the genetic defect, the properties studied, i.e., th e voltage-gated Ca currents and responses to serotonin and the choline rgic analog carbachol, resembled the effects observed in adrenalectomi zed mice, i.e., when no steroid receptors are activated. This may poin t to the necessity of functional GRs for the development of MR-induced actions. Ca current amplitude and transmitter responses in the hetero zygous animals,which combine a reduced amount of GRs in the hippocampu s with relatively high circulating levels of corticosterone, were larg e compared with those in the wild-type controls; this resembles the re sponses that were observed previously in rats subjected to a very high dose of corticosterone. These findings exemplify the use of GR knocko ut mice for the study of cellular properties in the brain. Further sub stantiation of the observations, however, awaits the development of si te-specific, inducible GR knockouts.