Rapid, experience-dependent translation of neurogranin enables memory encoding
Experience induces de novo protein synthesis in the brain and protein synthesis is required for long-term memory. It is important to define the critical temporal window of protein synthesis and identify newly synthesized proteins required for memory formation. Using a behavioral paradigm that tempor...
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| Format: | Article |
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National Academy of Sciences (U.S.)
2019
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| Online Access: | http://hdl.handle.net/1721.1/120292 https://orcid.org/0000-0002-3857-8671 https://orcid.org/0000-0002-6363-9579 https://orcid.org/0000-0003-0096-2288 |
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| author | Kuzniewska, Bozena Pena, Franciso X. Lei, Ding J. Nguyen, Shannon Dziembowska, Magdalena Jones, Kendrick Templet, Sebastian B. Zemoura, Khaled Hwang, Hongik Haensgen Saez, Henny M Saenz, Christopher Lewis, Michael C. Xu, Weifeng |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kuzniewska, Bozena Pena, Franciso X. Lei, Ding J. Nguyen, Shannon Dziembowska, Magdalena Jones, Kendrick Templet, Sebastian B. Zemoura, Khaled Hwang, Hongik Haensgen Saez, Henny M Saenz, Christopher Lewis, Michael C. Xu, Weifeng |
| author_sort | Kuzniewska, Bozena |
| collection | MIT |
| description | Experience induces de novo protein synthesis in the brain and protein synthesis is required for long-term memory. It is important to define the critical temporal window of protein synthesis and identify newly synthesized proteins required for memory formation. Using a behavioral paradigm that temporally separates the contextual exposure from the association with fear, we found that protein synthesis during the transient window of context exposure is required for contextual memory formation. Among an array of putative activity-dependent translational neuronal targets tested, we identified one candidate, a schizophrenia-associated candidate mRNA, neurogranin (Ng, encoded by the Nrgn gene) responding to novel-context exposure. The Ng mRNA was recruited to the actively translating mRNA pool upon novel-context exposure, and its protein levels were rapidly increased in the hippocampus. By specifically blocking activity-dependent translation of Ng using virus-mediated molecular perturbation, we show that experience-dependent translation of Ng in the hippocampus is required for contextual memory formation. We further interrogated the molecular mechanism underlying the experience-dependent translation of Ng, and found that fragile-X mental retardation protein (FMRP) interacts with the 3′UTR of the Nrgn mRNA and is required for activity-dependent translation of Ng in the synaptic compartment and contextual memory formation. Our results reveal that FMRP-mediated, experience-dependent, rapid enhancement of Ng translation in the hippocampus during the memory acquisition enables durable context memory encoding. Keywords: hippocampus; contextual memory; dentate gyrus; ASD; schizophrenia |
| first_indexed | 2024-09-23T12:55:23Z |
| format | Article |
| id | mit-1721.1/120292 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T12:55:23Z |
| publishDate | 2019 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1202922022-09-28T10:58:31Z Rapid, experience-dependent translation of neurogranin enables memory encoding Kuzniewska, Bozena Pena, Franciso X. Lei, Ding J. Nguyen, Shannon Dziembowska, Magdalena Jones, Kendrick Templet, Sebastian B. Zemoura, Khaled Hwang, Hongik Haensgen Saez, Henny M Saenz, Christopher Lewis, Michael C. Xu, Weifeng Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Department of Chemistry McGovern Institute for Brain Research at MIT Picower Institute for Learning and Memory Jones, Kendrick Templet, Sebastian B. Zemoura, Khaled Hwang, Hongik Haensgen Saez, Henny M Saenz, Christopher Lewis, Michael C. Xu, Weifeng Experience induces de novo protein synthesis in the brain and protein synthesis is required for long-term memory. It is important to define the critical temporal window of protein synthesis and identify newly synthesized proteins required for memory formation. Using a behavioral paradigm that temporally separates the contextual exposure from the association with fear, we found that protein synthesis during the transient window of context exposure is required for contextual memory formation. Among an array of putative activity-dependent translational neuronal targets tested, we identified one candidate, a schizophrenia-associated candidate mRNA, neurogranin (Ng, encoded by the Nrgn gene) responding to novel-context exposure. The Ng mRNA was recruited to the actively translating mRNA pool upon novel-context exposure, and its protein levels were rapidly increased in the hippocampus. By specifically blocking activity-dependent translation of Ng using virus-mediated molecular perturbation, we show that experience-dependent translation of Ng in the hippocampus is required for contextual memory formation. We further interrogated the molecular mechanism underlying the experience-dependent translation of Ng, and found that fragile-X mental retardation protein (FMRP) interacts with the 3′UTR of the Nrgn mRNA and is required for activity-dependent translation of Ng in the synaptic compartment and contextual memory formation. Our results reveal that FMRP-mediated, experience-dependent, rapid enhancement of Ng translation in the hippocampus during the memory acquisition enables durable context memory encoding. Keywords: hippocampus; contextual memory; dentate gyrus; ASD; schizophrenia 2019-02-08T16:47:32Z 2019-02-08T16:47:32Z 2018-06 2017-09 2019-02-08T16:06:46Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/120292 Jones, Kendrick J. et al. “Rapid, Experience-Dependent Translation of Neurogranin Enables Memory Encoding.” Proceedings of the National Academy of Sciences 115, 25 (June 2018): E5805–E5814 © 2018 National Academy of Sciences https://orcid.org/0000-0002-3857-8671 https://orcid.org/0000-0002-6363-9579 https://orcid.org/0000-0003-0096-2288 http://dx.doi.org/10.1073/pnas.1716750115 Proceedings of the National Academy of Sciences 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 National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Kuzniewska, Bozena Pena, Franciso X. Lei, Ding J. Nguyen, Shannon Dziembowska, Magdalena Jones, Kendrick Templet, Sebastian B. Zemoura, Khaled Hwang, Hongik Haensgen Saez, Henny M Saenz, Christopher Lewis, Michael C. Xu, Weifeng Rapid, experience-dependent translation of neurogranin enables memory encoding |
| title | Rapid, experience-dependent translation of neurogranin enables memory encoding |
| title_full | Rapid, experience-dependent translation of neurogranin enables memory encoding |
| title_fullStr | Rapid, experience-dependent translation of neurogranin enables memory encoding |
| title_full_unstemmed | Rapid, experience-dependent translation of neurogranin enables memory encoding |
| title_short | Rapid, experience-dependent translation of neurogranin enables memory encoding |
| title_sort | rapid experience dependent translation of neurogranin enables memory encoding |
| url | http://hdl.handle.net/1721.1/120292 https://orcid.org/0000-0002-3857-8671 https://orcid.org/0000-0002-6363-9579 https://orcid.org/0000-0003-0096-2288 |
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