Long-term memory deficits in pavlovian fear conditioning in Ca 2+/calmodulin kinase kinase α-deficient mice

Frank Blaeser, Matthew J. Sanders, Nga Truong, Shanelle Ko, Jun Wu Long, David F. Wozniak, Michael S. Fanselow, Min Zhuo, Talal A. Chatila

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Signaling by the Ca2+/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase α (CaMKKα) 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. CaMKKα 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 CaMKKα mutants exhibited normal long-term potentiation and normal levels of anxiety-like behavior. These results demonstrate a selective role for CaMKKα in contextual fear memory and suggest that different combinations of upstream and downstream components of the CaMK cascade may serve distinct physiological functions.

Original languageEnglish (US)
Pages (from-to)9105-9115
Number of pages11
JournalMolecular and cellular biology
Volume26
Issue number23
DOIs
StatePublished - Dec 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Blaeser, F., Sanders, M. J., Truong, N., Ko, S., Long, J. W., Wozniak, D. F., Fanselow, M. S., Zhuo, M., & Chatila, T. A. (2006). Long-term memory deficits in pavlovian fear conditioning in Ca 2+/calmodulin kinase kinase α-deficient mice. Molecular and cellular biology, 26(23), 9105-9115. https://doi.org/10.1128/MCB.01452-06