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GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal

Nature Neuroscience volume 16, pages 14361444 (2013) | Download Citation

Abstract

Fear renewal, a widely pursued model of post-traumatic stress disorder and phobias, refers to the context-specific relapse of conditioned fear after extinction. However, its molecular mechanisms are largely unknown. We found that renewal-inducing stimuli, generally believed to be insufficient to induce synaptic plasticity, enhanced excitatory synaptic strength, activity of synaptic GluA2-lacking AMPA receptors and Ser831 phosphorylation of synaptic surface GluA1 in the lateral nucleus of the amygdala (LAn) of fear-extinguished rats. Consistently, the induction threshold for LAn synaptic potentiation was considerably lowered after extinction, and renewal occluded this low-threshold potentiation. The low-threshold potentiation (a potential cellular substrate for renewal), but not long-term potentiation, was attenuated by dialysis into LAn neurons of a GluA1-derived peptide that competes with Ser831-phosphorylated GluA1. Microinjections of the same peptide into the LAn attenuated fear renewal, but not fear learning. Our findings suggest that GluA1 phosphorylation constitutes a promising target for clinical treatment of aberrant fear-related disorders.

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Acknowledgements

This paper is dedicated in loving memory to Sang-Soon Choi. We thank P. Sah for his valuable comments on our manuscript. This work was supported by a National Research Foundation of Korea grant funded by the Ministry of Education, Science and Technology (No. 2011-0018209, S.C.), by the Original Technology Research Program for Brain Science through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (No. 2011-0019226, S.C.) and by the Korean World Class Institute program (C.J.L.). B.S., Jeongyeon Kim, K.P., I.H., B.A., S.S., J.L., S.P. and Jihye Kim were supported by Brain Korea 21 Research Fellowships from the Korean Ministry of Education.

Author information

Author notes

    • Sukwon Lee
    • , Beomjong Song
    •  & Jeongyeon Kim

    These authors contributed equally to this work.

Affiliations

  1. School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.

    • Sukwon Lee
    • , Beomjong Song
    • , Ingie Hong
    • , Bobae An
    • , Sangho Song
    • , Jiwon Lee
    • , Sungmo Park
    • , Jihye Kim
    • , Dongeun Park
    • , Kyungjin Kim
    •  & Sukwoo Choi
  2. Center for Neural Science and Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, Korea.

    • Jeongyeon Kim
    •  & C Justin Lee
  3. Department of Biology, Kyunghee University, Seoul, Korea.

    • Kyungjoon Park
    •  & Ki Soon Shin
  4. Department of Life and Nanopharmaceutical Sciences, Kyunghee University, Seoul, Korea.

    • Kyungjoon Park
    •  & Ki Soon Shin
  5. Department of Physiology and Neuroscience, Neuroscience Institute, New York University Langone Medical Center, New York, New York, USA.

    • Richard W Tsien

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Contributions

S.L., B.S., Jeongyeon Kim, K.K., K.S.S. and S.C. designed the experiments. S.L., B.S., Jeongyeon Kim, K.P., I.H., B.A., S.S., J.L., S.P. and Jihye Kim performed the experiments. S.L., B.S., Jeongyeon Kim, K.K., K.S.S., R.W.T. and S.C. analyzed the data. S.L., B.S., Jeongyeon Kim, D.P., C.J.L., K.K., K.S.S., R.W.T. and S.C. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Kyungjin Kim or Ki Soon Shin or Sukwoo Choi.

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DOI

https://doi.org/10.1038/nn.3491

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