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Long-term memory deficits in Pavlovian fear conditioning in Ca2+/calmodulin kinase kinase alpha-deficient mice.

Signaling by the Ca(2+)/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase alpha (CaMKKalpha) isoform is an upstream component of the CaMK cascade whose function in different behavioral and learning and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKalpha mutants exhibited normal long-term spatial memory formation and cued fear conditioning but showed deficits in context fear during both conditioning and long-term follow-up testing. They also exhibited impaired activation of the downstream kinase CaMKIV/Gr and its substrate, the transcription factor cyclic AMP-responsive element binding protein (CREB) upon fear conditioning. Unlike CaMKIV/Gr-deficient mice, the CaMKKalpha mutants exhibited normal long-term potentiation and normal levels of anxiety-like behavior. These results demonstrate a selective role for CaMKKalpha in contextual fear memory and suggest that different combinations of upstream and downstream components of the CaMK cascade may serve distinct physiological functions.

Pubmed ID: 17015467

Authors

  • Blaeser F
  • Sanders MJ
  • Truong N
  • Ko S
  • Wu LJ
  • Wozniak DF
  • Fanselow MS
  • Zhuo M
  • Chatila TA

Journal

Molecular and cellular biology

Publication Data

December 19, 2006

Associated Grants

  • Agency: NIA NIH HHS, Id: P50 AG 05681
  • Agency: NIMH NIH HHS, Id: R01 MH 62122

Mesh Terms

  • Animals
  • Base Sequence
  • Behavior, Animal
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase
  • Conditioning, Classical
  • Electrophysiology
  • Fear
  • Hippocampus
  • Long-Term Potentiation
  • Male
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Protein-Serine-Threonine Kinases