title: Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice.
abstract: The Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca(2+) signaling; its function was analyzed by targeted gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP-responsive element binding protein (CREB) phosphorylation and Ca(2+)/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late phase of long-term depression in cerebellar Purkinje neurons. However, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits in spatial learning and memory. These results support an important role for CaMKIV/Gr in Ca(2+)-regulated neuronal gene transcription and synaptic plasticity and suggest that the contribution of other signaling pathways may spare spatial memory of CaMKIV/Gr-deficient mice.
authors.affiliation: Department of Pediatrics, the Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ho
authors.forename: J A
authors.initials: JA
authors.lastname: Liauw
authors.forename: F
authors.initials: F
authors.lastname: Blaeser
authors.forename: F
authors.initials: F
authors.lastname: Wei
authors.forename: S
authors.initials: S
authors.lastname: Hanissian
authors.forename: L M
authors.initials: LM
authors.lastname: Muglia
authors.forename: D F
authors.initials: DF
authors.lastname: Wozniak
authors.forename: A
authors.initials: A
authors.lastname: Nardi
authors.forename: K L
authors.initials: KL
authors.lastname: Arvin
authors.forename: D M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: D J
authors.initials: DJ
authors.lastname: Linden
authors.forename: M
authors.initials: M
authors.lastname: Zhuo
authors.forename: L J
authors.initials: LJ
authors.lastname: Muglia
authors.forename: T A
authors.initials: TA
authors.lastname: Chatila
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004558:Electric Stimulation; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011187:Posture; D011689:Purkinje Cells / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013550:Swimming; D013569:Synapses / Q000502:physiology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517685:Camk4 protein, mouse