Rapid, experience-dependent translation of neurogranin enables memory encoding.

Abstract

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.

• Authors: Kendrick J Jones, Sebastian Templet, Khaled Zemoura, Bozena Kuzniewska, Franciso X Pena, Hongik Hwang, Ding J Lei, Henny Haensgen, Shannon Nguyen, Christopher Saenz, Michael Lewis, Magdalena Dziembowska, Weifeng Xu
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 115 Issue 25 Pg. E5805-E5814 (06 19 2018) ISSN: 1091-6490 [Electronic] United States
• PMID: 29880715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 the Author(s). Published by PNAS.

Chemical References

• RNA, Messenger
• Neurogranin
• Fragile X Mental Retardation Protein

Topics

• Animals
• Fear (physiology)
• Fragile X Mental Retardation Protein (metabolism)
• Hippocampus (metabolism, physiology)
• Male
• Memory (physiology)
• Mice
• Mice, Inbred C57BL
• Neurogranin (metabolism)
• Neurons (metabolism, physiology)
• Protein Biosynthesis (physiology)
• RNA, Messenger (metabolism)