Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway
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...
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| Language: | en_US |
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Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/69083 https://orcid.org/0000-0002-7203-4299 https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0001-8426-6188 |
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| author | 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 Su, S. Joseph, Nadine F. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences 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 Su, S. Joseph, Nadine F. |
| author_sort | Zhu, J. Julius |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:14:17Z |
| format | Article |
| id | mit-1721.1/69083 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:14:17Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/690832022-09-30T00:37:50Z Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway 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 Su, S. Joseph, Nadine F. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Koch Institute for Integrative Cancer Research at MIT Tsai, Li-Huei Carr, Steven A. Guan, Ji-Song Su, Susan Chih-Chieh Gao, Jun Joseph, Nadine Xie, Zhigang Zhou, Ying Durak, Omer Tsai, Li-Huei 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. Norman B. Leventhal Fellowship United States. National Institutes of Health (NIH T32 MH074249) United States. National Institutes of Health (NIH RO1 NS051874) 2012-02-10T18:10:21Z 2012-02-10T18:10:21Z 2011-09 2011-06 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/69083 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. https://orcid.org/0000-0002-7203-4299 https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0001-8426-6188 en_US http://dx.doi.org/10.1371/journal.pone.0025735 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | 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 Su, S. Joseph, Nadine F. Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway |
| title | Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway |
| title_full | Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway |
| title_fullStr | Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway |
| title_full_unstemmed | Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway |
| title_short | Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway |
| title_sort | cdk5 is required for memory function and hippocampal plasticity via the camp signaling pathway |
| url | http://hdl.handle.net/1721.1/69083 https://orcid.org/0000-0002-7203-4299 https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0001-8426-6188 |
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