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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

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

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.[1]

References

  1. Regulation of contextual fear conditioning by baseline and inducible septo-hippocampal cyclin-dependent kinase 5. Fischer, A., Sananbenesi, F., Schrick, C., Spiess, J., Radulovic, J. Neuropharmacology (2003) [Pubmed]
 
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