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Persistent activation of central amygdala CRF neurons helps drive the immediate fear extinction deficit

Author

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  • Yong S. Jo

    (University of Washington
    Korea University)

  • Vijay Mohan K. Namboodiri

    (University of Washington)

  • Garret D. Stuber

    (University of Washington
    University of Washington)

  • Larry S. Zweifel

    (University of Washington
    University of Washington)

Abstract

Fear extinction is an active learning process whereby previously established conditioned responses to a conditioned stimulus are suppressed. Paradoxically, when extinction training is performed immediately following fear acquisition, the extinction memory is weakened. Here, we demonstrate that corticotrophin-releasing factor (CRF)-expressing neurons in the central amygdala (CeA) antagonize the extinction memory following immediate extinction training. CeA-CRF neurons transition from responding to the unconditioned stimulus to the conditioned stimulus during the acquisition of a fear memory that persists during immediate extinction training, but diminishes during delayed extinction training. Inhibition of CeA-CRF neurons during immediate extinction training is sufficient to promote enhanced extinction memories, and activation of these neurons following delay extinction training is sufficient to reinstate a previously extinguished fear memory. These results demonstrate CeA-CRF neurons are an important substrate for the persistence of fear and have broad implications for the neural basis of persistent negative affective behavioral states.

Suggested Citation

  • Yong S. Jo & Vijay Mohan K. Namboodiri & Garret D. Stuber & Larry S. Zweifel, 2020. "Persistent activation of central amygdala CRF neurons helps drive the immediate fear extinction deficit," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14393-y
    DOI: 10.1038/s41467-020-14393-y
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    Cited by:

    1. Matthew T. Birnie & Annabel K. Short & Gregory B. Carvalho & Lara Taniguchi & Benjamin G. Gunn & Aidan L. Pham & Christy A. Itoga & Xiangmin Xu & Lulu Y. Chen & Stephen V. Mahler & Yuncai Chen & Talli, 2023. "Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Camila Demaestri & Margaux Pisciotta & Naira Altunkeser & Georgia Berry & Hannah Hyland & Jocelyn Breton & Anna Darling & Brenna Williams & Kevin G. Bath, 2024. "Central amygdala CRF+ neurons promote heightened threat reactivity following early life adversity in mice," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Saurabh Thapliyal & Isabel Beets & Dominique A. Glauser, 2023. "Multisite regulation integrates multimodal context in sensory circuits to control persistent behavioral states in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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