Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment
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 regul...
| Main Authors: | , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Society for Neuroscience
2015
|
| Online Access: | http://hdl.handle.net/1721.1/98036 https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0001-8426-6188 |
| _version_ | 1826203351039082496 |
|---|---|
| author | Rudenko, Andrii Seo, Jinsoo Hu, Ji Su, Susan C. de Anda, Froylan Calderon Durak, Omer Ericsson, Maria Carlen, Marie 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 Rudenko, Andrii Seo, Jinsoo Hu, Ji Su, Susan C. de Anda, Froylan Calderon Durak, Omer Ericsson, Maria Carlen, Marie Tsai, Li-Huei |
| author_sort | Rudenko, Andrii |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:35:33Z |
| format | Article |
| id | mit-1721.1/98036 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:35:33Z |
| publishDate | 2015 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/980362022-09-28T08:49:40Z Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment Rudenko, Andrii Seo, Jinsoo Hu, Ji Su, Susan C. de Anda, Froylan Calderon Durak, Omer Ericsson, Maria Carlen, Marie Tsai, Li-Huei Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Rudenko, Andrii Seo, Jinsoo Hu, Ji Su, Susan C. de Anda, Froylan Calderon Durak, Omer Carlen, Marie Tsai, Li-Huei 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. National Alliance for Research on Schizophrenia and Depression (U.S.) (Young Investigator Award) National Institutes of Health (U.S.) (Grant RO1-NS051874-16) Simons Foundation (Autism Research Initiative Grant) 2015-08-05T16:09:10Z 2015-08-05T16:09:10Z 2015-02 2014-12 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/98036 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. https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0001-8426-6188 en_US http://dx.doi.org/10.1523/jneurosci.0969-14.2015 Journal of Neuroscience 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. application/pdf Society for Neuroscience Society for Neuroscience |
| spellingShingle | Rudenko, Andrii Seo, Jinsoo Hu, Ji Su, Susan C. de Anda, Froylan Calderon Durak, Omer Ericsson, Maria Carlen, Marie Tsai, Li-Huei Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment |
| title | Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment |
| title_full | Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment |
| title_fullStr | Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment |
| title_full_unstemmed | Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment |
| title_short | Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment |
| title_sort | loss of cyclin dependent kinase 5 from parvalbumin interneurons leads to hyperinhibition decreased anxiety and memory impairment |
| url | http://hdl.handle.net/1721.1/98036 https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0001-8426-6188 |
| work_keys_str_mv | AT rudenkoandrii lossofcyclindependentkinase5fromparvalbumininterneuronsleadstohyperinhibitiondecreasedanxietyandmemoryimpairment AT seojinsoo lossofcyclindependentkinase5fromparvalbumininterneuronsleadstohyperinhibitiondecreasedanxietyandmemoryimpairment AT huji lossofcyclindependentkinase5fromparvalbumininterneuronsleadstohyperinhibitiondecreasedanxietyandmemoryimpairment AT sususanc lossofcyclindependentkinase5fromparvalbumininterneuronsleadstohyperinhibitiondecreasedanxietyandmemoryimpairment AT deandafroylancalderon lossofcyclindependentkinase5fromparvalbumininterneuronsleadstohyperinhibitiondecreasedanxietyandmemoryimpairment AT durakomer lossofcyclindependentkinase5fromparvalbumininterneuronsleadstohyperinhibitiondecreasedanxietyandmemoryimpairment AT ericssonmaria lossofcyclindependentkinase5fromparvalbumininterneuronsleadstohyperinhibitiondecreasedanxietyandmemoryimpairment AT carlenmarie lossofcyclindependentkinase5fromparvalbumininterneuronsleadstohyperinhibitiondecreasedanxietyandmemoryimpairment AT tsailihuei lossofcyclindependentkinase5fromparvalbumininterneuronsleadstohyperinhibitiondecreasedanxietyandmemoryimpairment |