Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway
Name
Guan-2011-Cdk5 Is Required for.pdf
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2.24 MB
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Author(s)
Zhu, J. Julius
Clauser, Karl R.
Guan, Ji-Song
Gao, Jun
Xie, Zhigang
Zhou, Ying
Durak, Omer
Tsai, Li-Huei
Zhang, Lei, Ph. D Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, fl. 2014.
Carr, Steven A
Date Issued
September 2011
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Guan, Ji-Song et al. “Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway.” Ed. Brahim Nait-Oumesmar. PLoS ONE 6.9 (2011): e25735. Web. 10 Feb. 2012.
Version
Final published version
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 inhibitor that prevents cAMP depletion, restores synaptic plasticity and memory formation in Cdk5-deficient mice. Collectively, our results demonstrate a critical role for Cdk5 in the regulation of cAMP-mediated hippocampal functions essential for synaptic plasticity and memory formation.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0025735
