Rapid, experience-dependent translation of neurogranin enables memory encoding

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

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageEnglish
Pages (from-to)E5805-E5814
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number25
DOIs
StatePublished - 19 Jun 2018

Keywords

  • ASD
  • Contextual memory
  • Dentate gyrus
  • Hippocampus
  • Schizophrenia

Fingerprint

Dive into the research topics of 'Rapid, experience-dependent translation of neurogranin enables memory encoding'. Together they form a unique fingerprint.

Cite this