ALTERED BEHAVIOR AND LONG-TERM POTENTIATION IN TYPE-I ADENYLYL-CYCLASE MUTANT MICE

The murine Ca2+-stimulated adenylyl cyclase (type I) (EC 4.6.1.1), whi ch is expressed predominantly in brain, was inactivated by targeted mu tagenesis. Ca2+ stimulated adenylyl cyclase activity was reduced 40-60 % in the hippocampus, neocortex, and cerebellum. Long-term potentiatio n in the CA1 region of the hippocampus from mutants was perturbed rela tive to controls. Both the initial slope and maximum extent of changes in synaptic response were reduced. Although mutant mice learned to fi nd a hidden platform in the Morris water task normally, they did not d isplay a preference for the region where the platform had been when it was removed. These results indicate that disruption of the gene for t he type I adenylyl cyclase produces changes in behavior and that the c AMP signal transduction pathway may play an important role in synaptic plasticity.