title: Cdk5/p35 functions as a crucial regulator of spatial learning and memory.
abstract: BACKGROUND
  Cyclin-dependent kinase 5 (Cdk5), which is activated by binding to p35 or p39, is involved in synaptic plasticity and affects learning and memory formation. In Cdk5 knockout (KO) mice and p35 KO mice, brain development is severely impaired because neuronal migration is impaired and lamination is disrupted. To avoid these developmental confounders, we generated inducible CreER-p35 conditional (cKO) mice to study the role of Cdk5/p35 in higher brain function.
  
  
  RESULTS
  CreER-p35 cKO mice exhibited spatial learning and memory impairments and reduced anxiety-like behavior. These phenotypes resulted from a decrease in the dendritic spine density of CA1 pyramidal neurons and defective long-term depression induction in the hippocampus.
  
  
  CONCLUSIONS
  Taken together, our findings reveal that Cdk5/p35 regulates spatial learning and memory, implicating Cdk5/p35 as a therapeutic target in neurological disorders.
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, , Shinjuku-ku, Tokyo, 162-8480, Japan. sprewell-tomo348@akane.waseda.jp.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Mishiba
authors.affiliation: Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, Saitama, 351-0198, Japan. mikatanaka@brain.riken.jp.
authors.forename: Mika
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, , Shinjuku-ku, Tokyo, 162-8480, Japan. mitanaoki@fuji.waseda.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Mita
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, , Shinjuku-ku, Tokyo, 162-8480, Japan. jane@suou.waseda.jp.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: He
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, , Shinjuku-ku, Tokyo, 162-8480, Japan. amethyst-ks.46@toki.waseda.jp.
authors.forename: Kodai
authors.initials: K
authors.lastname: Sasamoto
authors.affiliation: Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, Saitama, 351-0198, Japan. sitohara@brain.riken.jp.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, , Shinjuku-ku, Tokyo, 162-8480, Japan. ohshima@waseda.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D051360:Cyclin-Dependent Kinase 5 / Q000172:deficiency / Q000378:metabolism*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D008568:Memory; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D010770:Phosphotransferases / Q000172:deficiency / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D065853:Spatial Learning; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C492236:Cdk5r1 protein, mouse; D011960:Receptors, Estrogen; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D013629:Tamoxifen; D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; C045073:Cre recombinase; D019426:Integrases