Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway

2011

Cdk5's Role in Memory and Synaptic Plasticity

Sample size: 16 publication 10 minutes Evidence: high

Author Information

Author(s): Guan Ji-Song, Su Susan C., Gao Jun, Joseph Nadine, Xie Zhigang, Zhou Ying, Durak Omer, Zhang Lei, Zhu J. Julius, Clauser Karl R., Carr Steven A., Tsai Li-Huei

Primary Institution: Massachusetts Institute of Technology

Hypothesis

Cdk5 is essential for memory function and hippocampal plasticity via the cAMP signaling pathway.

Conclusion

Cdk5 is critical for regulating cAMP-mediated hippocampal functions necessary for synaptic plasticity and memory formation.

Supporting Evidence

Cdk5 loss of function in hippocampal circuits results in severe impairments in memory formation and retrieval.
Rolipram, a PDE4 inhibitor, restores synaptic plasticity and memory formation in Cdk5-deficient mice.
Dysregulation of cAMP is associated with defective CREB phosphorylation in Cdk5-deficient mice.
Cdk5 is involved in the modulation of phosphodiesterase expression affecting cAMP signaling.
Impaired long-term potentiation (LTP) and long-term depression (LTD) were observed in Cdk5 mutant mice.
Memory deficits in Cdk5f/f/T29 mice were significantly improved with rolipram treatment.
Immunostaining showed reduced Cdk5 levels in the CA1 region of the hippocampus in Cdk5f/f/T29 mice.
Behavioral tests indicated that Cdk5 is crucial for both associative and spatial memory.