Cdk5/p35 functions as a crucial regulator of spatial learning and memory

Tomohide Mishiba, Mika Tanaka, Naoki Mita, Xiaojuan He, Kodai Sasamoto, Shigeyoshi Itohara, Toshio Ohshima*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


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.

Original languageEnglish
Article number82
JournalMolecular brain
Issue number1
Publication statusPublished - 2014


  • Hippocampus
  • Kinase
  • Memory
  • Spatial learning
  • Synaptic plasticity

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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