Regulation of contextual fear conditioning by baseline and inducible septo-hippocampal cyclin-dependent kinase 5

André Fischer, Farahnaz Sananbenesi, Christina Schrick, Joachim Spiess, Jelena Radulovic

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

In this work, we confirm the novel role of cyclin-dependent kinase (Cdk) 5 in associative learning by demonstrating that injection of the Cdk5 inhibitor butyrolactone I into the lateral septum or hippocampus profoundly impaired context-dependent fear conditioning of C57BL/6J mice. However, unlike the inducible up-regulation of Cdk5 and its regulator p35 observed in Balb/c mice, high baseline levels, which were not affected by fear conditioning, were found in C57BL/6J mice. Surprisingly, microinjections of butyrolactone I into the lateral septum or hippocampus significantly decreased baseline Cdk5 activity within the entire septo-hippocampal circuitry, suggesting a functional link between septal and hippocampal Cdk5 activity. Significantly higher levels of the transcription factor Sp4 in the septo-hippocampal system of C57BL/6J mice may account for the high baseline Cdk5/p35 production. On the other hand, the stronger cFos production observed in the lateral septum of fear conditioned Balb/c mice may be responsible, at least in part, for the inducible up-regulation of Cdk5 in this strain. These results suggest that the role of Cdk5 in memory consolidation is strain independent and functionally related to the septo-hippocampal circuitry. However, the molecular regulation of baseline and inducible Cdk5 protein might be different among individual mouse strains and possibly other species.

Original languageEnglish (US)
Pages (from-to)1089-1099
Number of pages11
JournalNeuropharmacology
Volume44
Issue number8
DOIs
StatePublished - Jun 2003
Externally publishedYes

Keywords

  • Cyclin-dependent kinase 5
  • Fear conditioning
  • Hippocampus
  • Septum
  • Sp4
  • cFos

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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