Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment
Author(s)Rudenko, Andrii; Seo, Jinsoo; Hu, Ji; Su, Susan C.; de Anda, Froylan Calderon; Durak, Omer; Ericsson, Maria; Carlen, Marie; Tsai, Li-Huei; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory
Journal of Neuroscience
Society for Neuroscience
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.
Final published version