Rapid, experience-dependent translation of neurogranin enables memory encoding
| Autor: | Kendrick J. Jones, Hongik Hwang, Bozena Kuzniewska, Franciso X Pena, Magdalena Dziembowska, Ding J Lei, Shannon Nguyen, Christopher Saenz, Khaled Zemoura, Sebastian Templet, Michael C. Lewis, Henny Haensgen, Weifeng Xu |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine contextual memory hippocampus Context-dependent memory education Biology ASD Fragile X Mental Retardation Protein Mice 03 medical and health sciences 0302 clinical medicine Memory Encoding (memory) Protein biosynthesis Animals RNA Messenger dentate gyrus Neurogranin Gene Neurons Messenger RNA Multidisciplinary Dentate gyrus Fear Biological Sciences Mice Inbred C57BL schizophrenia 030104 developmental biology PNAS Plus Protein Biosynthesis Contextual memory Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance De novo protein synthesis is critical for memory formation. We found that protein synthesis during acquisition is transiently required for contextual memory formation. We identified one candidate gene, Nrgn (encoding protein neurogranin, Ng) with enhanced translation upon novel-context exposure, and found that experience-dependent translation of Ng in the hippocampus is required for contextual memory formation. Furthermore, fragile-X mental retardation protein interacts with the 3′UTR of the Nrgn mRNA, which is required for activity-dependent translation of Ng in the synaptic compartment and contextual memory formation. Together, these results indicate that experience-dependent and acute translation of Ng in the hippocampus during memory acquisition enables durable context 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 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. |
| Databáze: | OpenAIRE |
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