Encoding of Contextual Fear Memory Requires De Novo Proteins in the Prelimbic Cortex

  • Author Footnotes
    1 VR, KT, BLR, and SS contributed equally to this work.
    Valerio Rizzo
    Footnotes
    1 VR, KT, BLR, and SS contributed equally to this work.
    Affiliations
    Department of Neuroscience, the Scripps Research Institute, Center for Complex Systems & Brain Sciences, College of Science, Florida Atlantic University, Jupiter, Florida
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  • Author Footnotes
    1 VR, KT, BLR, and SS contributed equally to this work.
    Khalid Touzani
    Footnotes
    1 VR, KT, BLR, and SS contributed equally to this work.
    Affiliations
    Department of Neuroscience, the Scripps Research Institute, Center for Complex Systems & Brain Sciences, College of Science, Florida Atlantic University, Jupiter, Florida
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  • Author Footnotes
    1 VR, KT, BLR, and SS contributed equally to this work.
    Bindu L. Raveendra
    Footnotes
    1 VR, KT, BLR, and SS contributed equally to this work.
    Affiliations
    Department of Neuroscience, the Scripps Research Institute, Center for Complex Systems & Brain Sciences, College of Science, Florida Atlantic University, Jupiter, Florida
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  • Author Footnotes
    1 VR, KT, BLR, and SS contributed equally to this work.
    Supriya Swarnkar
    Footnotes
    1 VR, KT, BLR, and SS contributed equally to this work.
    Affiliations
    Department of Neuroscience, the Scripps Research Institute, Center for Complex Systems & Brain Sciences, College of Science, Florida Atlantic University, Jupiter, Florida
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  • Joan Lora
    Affiliations
    Department of Psychology, Center for Complex Systems & Brain Sciences, College of Science, Florida Atlantic University, Jupiter, Florida
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  • Beena M. Kadakkuzha
    Affiliations
    Department of Neuroscience, the Scripps Research Institute, Center for Complex Systems & Brain Sciences, College of Science, Florida Atlantic University, Jupiter, Florida
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  • Xin-An Liu
    Affiliations
    Department of Neuroscience, the Scripps Research Institute, Center for Complex Systems & Brain Sciences, College of Science, Florida Atlantic University, Jupiter, Florida
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  • Chao Zhang
    Affiliations
    Department of Medicine and Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York
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  • Doron Betel
    Affiliations
    Department of Medicine and Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York
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  • Robert W. Stackman
    Affiliations
    Department of Psychology, Center for Complex Systems & Brain Sciences, College of Science, Florida Atlantic University, Jupiter, Florida
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  • Sathyanarayanan V. Puthanveettil
    Correspondence
    Address correspondence to Sathyanarayanan V. Puthanveettil, Department of Neuroscience, the Scripps Research Institute, 130 Scripps Way, Jupiter FL 33458; .
    Affiliations
    Department of Neuroscience, the Scripps Research Institute, Center for Complex Systems & Brain Sciences, College of Science, Florida Atlantic University, Jupiter, Florida
    Search for articles by this author
  • Author Footnotes
    1 VR, KT, BLR, and SS contributed equally to this work.
Published:October 21, 2016DOI:https://doi.org/10.1016/j.bpsc.2016.10.002

      Abstract

      Background

      Despite our understanding of the significance of the prefrontal cortex in the consolidation of long-term memories, its role in the encoding of long-term memories remains elusive. Here we investigated the role of new protein synthesis in the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory.

      Methods

      Because a change in the association of messenger RNAs (mRNAs) to polyribosomes is an indicator of new protein synthesis, we assessed the changes in polyribosome-associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse. Differential gene expression in the mPFC was identified by polyribosome profiling (n = 18). The role of new protein synthesis in the mPFC was determined by focal inhibition of protein synthesis (n = 131) and by intraprelimbic cortex manipulation (n = 56) of Homer3, a candidate identified from polyribosome profiling.

      Results

      We identified several mRNAs that are differentially and temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of protein synthesis in the prelimbic (PL) cortex but not in the anterior cingulate cortex region of the mPFC immediately after CFC disrupted encoding of contextual fear memory. Intriguingly, inhibition of new protein synthesis in the PL cortex 6 hours after CFC did not impair encoding. Furthermore, expression of Homer3, an mRNA enriched in polyribosomes following CFC, in the PL cortex constrained encoding of contextual fear memory.

      Conclusions

      Our studies identify several molecular substrates of new protein synthesis in the mPFC and establish that encoding of contextual fear memories require new protein synthesis in PL subregion of mPFC.

      Keywords

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