Abstract
BackgroundCyclin-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.ResultsCreER-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.ConclusionsTaken together, our findings reveal that Cdk5/p35 regulates spatial learning and memory, implicating Cdk5/p35 as a therapeutic target in neurological disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-014-0082-x) contains supplementary material, which is available to authorized users.
Highlights
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
Biochemical analysis revealed no alteration of NR2B protein in the hippocampi of CreER-p35 conditional knockout (cKO) mice. These findings indicate that the kinase function of Cdk5/p35 is essential for normal synaptic function and spatial learning and memory
Reduction in dendritic spine density in CreER-p35 cKO mice To clarify the mechanism underlying the impairment in spatial learning and memory, we studied the morphology of Golgi-stained pyramidal neurons in the hippocampal area CA1 and layer V in the cerebral cortex
Summary
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. Inducible Cdk conditional knockout (cKO) mice show enhanced synaptic plasticity and improved spatial learning and memory via an increase in synaptic NR2B subunits of NMDA receptors [13]. It was shown that disrupting long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal CA1 of mice lacking Cdk results in the impairment of spatial learning and memory partly due to the collapse of cAMP signaling [14]. These two results, are likely secondary consequences of the loss of Cdk function as a scaffold protein [15] and a regulator of other signaling pathways, respectively. The original functions of Cdk in synaptic plasticity and in the phosphorylation of synaptic proteins remain to be elucidated
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