Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment
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Author(s)
Su, Susan Chih-Chieh
Rudenko, Andrii
Cho, Sukhee
Tsai, Li-Huei
Date Issued
July 2013
Journal
Neurobiology of Learning and Memory
Publisher
Elsevier
Citation
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
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.NLM.2013.06.016
