Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice.
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.
Ho
N
N
Department of Pediatrics, the Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Liauw
J A
JA
Blaeser
F
F
Wei
F
F
Hanissian
S
S
Muglia
L M
LM
Wozniak
D F
DF
Nardi
A
A
Arvin
K L
KL
Holtzman
D M
DM
Linden
D J
DJ
Zhuo
M
M
Muglia
L J
LJ
Chatila
T A
TA
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*
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