Evidence that the type I adenylyl cyclase may be important for neuroplasticity: Mutant mice deficient in the gene for type I adenylyl cyclase show altered behavior and LTP

Abstract

AbstractThe regulatory properties of the neurospecific, type I adenylyl cyclase and its distribution within brain have suggested that this enzyme may be important for neuroplasticity. To address this issue, the murine, Ca2+-stimulated adenylyl cyclase (type I), was inactivated by targeted mutagenesis. Ca2+-stimulated adenylyl cyclase activity was reduced 40% to 60% in the hippocampus, neocortex, and cerebellum. Long term potentiation in the CA1 region of the hippocampus from mutants was perturbed relative to controls. Both the initial slope and maxim um extent of changes in synaptic response were reduced. Although mutant mice learned to find a hidden platform normally in the Morris water task, they did not display a preference for the region where the platform had been when it was removed. The behavioral phenotype of these mice is very similar to that exhibited by mice which have been surgically lesioned in the hippocampus. These results indicate that disruption of the gene for the type I adenylyl cyclase produces changes in spatial memory and indicate that the cAMP signal transduction pathway may play an important role for synaptic plasticity.