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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.

Pubmed ID: 10964952


  • Ho N
  • Liauw JA
  • Blaeser F
  • Wei F
  • Hanissian S
  • Muglia LM
  • Wozniak DF
  • Nardi A
  • Arvin KL
  • Holtzman DM
  • Linden DJ
  • Zhuo M
  • Muglia LJ
  • Chatila TA


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

September 1, 2000

Associated Grants


Mesh Terms

  • Animals
  • Brain
  • Calcium Signaling
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cerebral Cortex
  • Cyclic AMP Response Element-Binding Protein
  • Electric Stimulation
  • Hippocampus
  • Long-Term Potentiation
  • Male
  • Maze Learning
  • Memory
  • Mice
  • Mice, Knockout
  • Motor Activity
  • Neuronal Plasticity
  • Neurons
  • Posture
  • Purkinje Cells
  • Pyramidal Cells
  • Reverse Transcriptase Polymerase Chain Reaction
  • Swimming
  • Synapses