Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment
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Rudenko-2015-Loss of Cyclin-Depen.pdf
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Author(s)
Rudenko, Andrii
Seo, Jinsoo
Hu, Ji
Su, Susan C.
de Anda, Froylan Calderon
Durak, Omer
Ericsson, Maria
Carlen, Marie
Tsai, Li-Huei
Date Issued
February 2015
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Rudenko, A., J. Seo, J. Hu, S. C. Su, F. C. de Anda, O. Durak, M. Ericsson, M. Carlen, and L.-H. Tsai. “Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment.” Journal of Neuroscience 35, no. 6 (February 11, 2015): 2372–2383.
Version
Final published version
Abstract
Perturbations in fast-spiking parvalbumin (PV) interneurons are hypothesized to be a major component of various neuropsychiatric disorders; however, the mechanisms regulating PV interneurons remain mostly unknown. Recently, cyclin-dependent kinase 5 (Cdk5) has been shown to function as a major regulator of synaptic plasticity. Here, we demonstrate that genetic ablation of Cdk5 in PV interneurons in mouse brain leads to an increase in GABAergic neurotransmission and impaired synaptic plasticity. PVCre;fCdk5 mice display a range of behavioral abnormalities, including decreased anxiety and memory impairment. Our results reveal a central role of Cdk5 expressed in PV interneurons in gating inhibitory neurotransmission and underscore the importance of such regulation during behavioral tasks. Our findings suggest that Cdk5 can be considered a promising therapeutic target in a variety of conditions attributed to inhibitory interneuronal dysfunction, such as epilepsy, anxiety disorders, and schizophrenia.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1523/jneurosci.0969-14.2015
