title: Cyclin-dependent kinase 5 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 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.
authors.affiliation: Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, 37075 Goettingen, Germany. fischer@mail.em.mpg.de
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Sananbenesi
authors.forename: Christina
authors.initials: C
authors.lastname: Schrick
authors.forename: Joachim
authors.initials: J
authors.lastname: Spiess
authors.forename: Jelena
authors.initials: J
authors.lastname: Radulovic
mesh_terms: D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D002799:Cholinergic Fibers / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005080:Exercise Test; D005239:Fear / Q000502:physiology; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020665:Septum of Brain / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C082868:butyrolactone I; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases; D015107:4-Butyrolactone