Guan JS, Su SC, Gao J, Joseph N, Xie Z, Zhou Y, Durak O, Zhang L, Zhu JJ, Clauser KR, Carr SA, Tsai LH. Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway.PLoS One. 2011;6(9):e25735. Epub 2011 Sep 30.

Abstract Memory formation is modulated by pre- and post-synaptic signaling events in neurons. The neuronal protein kinase Cyclin-Dependent Kinase 5 (Cdk5) phosphorylates a variety of synaptic substrates and is implicated in memory formation. It has also been shown to play a role in homeostatic regulation of synaptic plasticity in cultured neurons. Surprisingly, we found that Cdk5 loss of function in hippocampal circuits results in severe impairments in memory formation and retrieval. Moreover, Cdk5 loss of function in the hippocampus disrupts cAMP signaling due to an aberrant increase in phosphodiesterase (PDE) proteins. Dysregulation of cAMP is associated with defective CREB phosphorylation and disrupted composition of synaptic proteins in Cdk5-deficient mice. Rolipram, a PDE4 inhibit......