Cyclin-Dependent Kinase 5 Is Required for Associative Learning

TLDR

Stressful experiences can persistently enhance learning, potentially via changes in gene expression. The study identifies differential expression of the Cdk5 gene in response to stress. The authors used subtractive hybridization to detect stress‑induced differential expression of Cdk5. Cdk5 is selectively induced in septohippocampal cholinergic neurons during stress, and its activity—blocked by butyrolactone I—is essential for acquiring conditioned fear, demonstrating that transient Cdk5 activity in this system is required for associative learning.

Abstract

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 <i>Cdk5</i> 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.