title: Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice.
abstract: The murine Ca(2+)-stimulated adenylyl cyclase (type I) (EC 4.6.1.1), which is expressed predominantly in brain, was inactivated by targeted mutagenesis. Ca(2+)-stimulated adenylyl cyclase activity was reduced 40-60% 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 maximum extent of changes in synaptic response were reduced. Although mutant mice learned to find a hidden platform in the Morris water task normally, they did not display a preference for the region where the platform had been when it was removed. These results indicate that disruption of the gene for the type I adenylyl cyclase produces changes in behavior and that the cAMP signal transduction pathway may play an important role in synaptic plasticity.
authors: Department of Pharmacology, Howard Hughes Medical Institute, University of Washington, Seattle 98195.
authors: Z L
authors: ZL
authors: Wu
authors: S A
authors: SA
authors: Thomas
authors: E C
authors: EC
authors: Villacres
authors: Z
authors: Z
authors: Xia
authors: M L
authors: ML
authors: Simmons
authors: C
authors: C
authors: Chavkin
authors: R D
authors: RD
authors: Palmiter
authors: D R
authors: DR
authors: Storm
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000502:physiology*; D001933:Brain Stem / Q000201:enzymology / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000201:enzymology / Q000502:physiology; D002540:Cerebral Cortex / Q000201:enzymology / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D005071:Evoked Potentials; D015698:Genomic Library; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology; D007700:Kinetics; D007858:Learning; D017774:Long-Term Potentiation; D051379:Mice; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015183:Restriction Mapping
chemical_list: D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium