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The Journal of Neuroscience, May 1, 2002, 22(9):3700-3707

Cyclin-Dependent Kinase 5 Is Required for Associative Learning

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

Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, 37075 Goettingen, Germany

Transient stressful experiences may persistently facilitate associative and nonassociative learning, possibly through alterations of gene expression. Here we identify, by subtractive hybridization, differential expression of the Cdk5 gene in response to stress. The Cdk5 protein is selectively induced in the fibers of septohippocampal cholinergic neurons but not in other regions of prominent Cdk5 production. This upregulation is accompanied by increased Cdk5 kinase activity, which is blocked completely by the Cdk5 inhibitor butyrolactone I. Microinjection of butyrolactone I into the lateral septum and hippocampus prevents the acquisition of conditioned context-dependent fear as well as its stress-induced facilitation. By demonstrating that a transient increase of Cdk5 activity within the septohippocampal system is required for associative learning, an important novel role of Cdk5 has been identified.

Key words: cyclin-dependent kinase 5; stress; fear conditioning; septum; hippocampus; cholinergic; mice

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2293700-08$05.00/0

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