Impaired Synaptic Plasticity and cAMP Response Element-Binding Protein Activation in Ca2+/calmodulin-dependent Protein Kinase Type IV/Gr-deficient Mice

J Neurosci. 2000 Sep 1;20(17):6459-72. doi: 10.1523/JNEUROSCI.20-17-06459.2000.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Camk4 protein, mouse