Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment
Cyclin-dependent kinase 5 (Cdk5) is associated with synaptic plasticity and cognitive function. Previous reports have demonstrated that Cdk5 is necessary for memory formation, although others have reported Cdk5 conditional knockout mouse models exhibiting enhanced learning and memory. Furthermore, h...
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| Format: | Article |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/112703 https://orcid.org/0000-0003-1262-0592 |
| _version_ | 1826210794588602368 |
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| author | Su, Susan Chih-Chieh Rudenko, Andrii Cho, Sukhee Tsai, Li-Huei |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Su, Susan Chih-Chieh Rudenko, Andrii Cho, Sukhee Tsai, Li-Huei |
| author_sort | Su, Susan Chih-Chieh |
| collection | MIT |
| description | Cyclin-dependent kinase 5 (Cdk5) is associated with synaptic plasticity and cognitive function. Previous reports have demonstrated that Cdk5 is necessary for memory formation, although others have reported Cdk5 conditional knockout mouse models exhibiting enhanced learning and memory. Furthermore, how Cdk5 acts in specific cell populations to affect behavior and cognitive outcomes remains unclear. Here we conduct a behavioral characterization of a forebrain-specific Cdk5 conditional knockout mouse model under the αCaMKII promoter, in which Cdk5 is ablated in excitatory pyramidal neurons of the forebrain. The Cdk5 conditional knockouts exhibit hyperactivity in the open field, reduced anxiety, and reduced behavioral despair. Moreover, the Cdk5 conditional knockouts also display impaired spatial learning in the Morris water maze and are severely impaired in contextual fear memory, which correspond to deficits in synaptic transmission. Remarkably, the hyperactivity of the Cdk5 conditional knockouts can be ameliorated by the administration of lithium chloride, an inhibitor of GSK3β signaling. Collectively, our data reveal that Cdk5 ablation from forebrain excitatory neurons results in deleterious effects on emotional and cognitive behavior and highlight a key role for Cdk5 in regulating the GSK3β signaling pathway. |
| first_indexed | 2024-09-23T14:55:34Z |
| format | Article |
| id | mit-1721.1/112703 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:55:34Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1127032022-09-29T11:29:14Z Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment Su, Susan Chih-Chieh Rudenko, Andrii Cho, Sukhee Tsai, Li-Huei Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Su, Susan Chih-Chieh Rudenko, Andrii Cho, Sukhee Tsai, Li-Huei Cyclin-dependent kinase 5 (Cdk5) is associated with synaptic plasticity and cognitive function. Previous reports have demonstrated that Cdk5 is necessary for memory formation, although others have reported Cdk5 conditional knockout mouse models exhibiting enhanced learning and memory. Furthermore, how Cdk5 acts in specific cell populations to affect behavior and cognitive outcomes remains unclear. Here we conduct a behavioral characterization of a forebrain-specific Cdk5 conditional knockout mouse model under the αCaMKII promoter, in which Cdk5 is ablated in excitatory pyramidal neurons of the forebrain. The Cdk5 conditional knockouts exhibit hyperactivity in the open field, reduced anxiety, and reduced behavioral despair. Moreover, the Cdk5 conditional knockouts also display impaired spatial learning in the Morris water maze and are severely impaired in contextual fear memory, which correspond to deficits in synaptic transmission. Remarkably, the hyperactivity of the Cdk5 conditional knockouts can be ameliorated by the administration of lithium chloride, an inhibitor of GSK3β signaling. Collectively, our data reveal that Cdk5 ablation from forebrain excitatory neurons results in deleterious effects on emotional and cognitive behavior and highlight a key role for Cdk5 in regulating the GSK3β signaling pathway. National Institutes of Health (U.S.) (Grant T32 MH074249) National Institutes of Health (U.S.) (Grant R01 NS051874) 2017-12-12T14:53:03Z 2017-12-12T14:53:03Z 2013-07 2017-12-11T20:44:06Z Article http://purl.org/eprint/type/JournalArticle 1074-7427 1095-9564 http://hdl.handle.net/1721.1/112703 Su, Susan C. et al. “Forebrain-Specific Deletion of Cdk5 in Pyramidal Neurons Results in Mania-Like Behavior and Cognitive Impairment.” Neurobiology of Learning and Memory 105 (October 2013): 54–62. © 2013 Elsevier https://orcid.org/0000-0003-1262-0592 http://dx.doi.org/10.1016/J.NLM.2013.06.016 Neurobiology of Learning and Memory Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Su, Susan Chih-Chieh Rudenko, Andrii Cho, Sukhee Tsai, Li-Huei Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment |
| title | Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment |
| title_full | Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment |
| title_fullStr | Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment |
| title_full_unstemmed | Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment |
| title_short | Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment |
| title_sort | forebrain specific deletion of cdk5 in pyramidal neurons results in mania like behavior and cognitive impairment |
| url | http://hdl.handle.net/1721.1/112703 https://orcid.org/0000-0003-1262-0592 |
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