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Central amygdala CRF+ neurons promote heightened threat reactivity following early life adversity in mice

Author

Listed:
  • Camila Demaestri

    (Columbia University)

  • Margaux Pisciotta

    (Barnard College of Columbia University)

  • Naira Altunkeser

    (Columbia University)

  • Georgia Berry

    (New York State Psychiatric Institute)

  • Hannah Hyland

    (New York State Psychiatric Institute)

  • Jocelyn Breton

    (New York State Psychiatric Institute
    Columbia University Irving Medical Center)

  • Anna Darling

    (Columbia University)

  • Brenna Williams

    (Columbia University)

  • Kevin G. Bath

    (New York State Psychiatric Institute
    Columbia University Irving Medical Center)

Abstract

Failure to appropriately predict and titrate reactivity to threat is a core feature of fear and anxiety-related disorders and is common following early life adversity (ELA). A population of neurons in the lateral central amygdala (CeAL) expressing corticotropin releasing factor (CRF) have been proposed to be key in processing threat of different intensities to mediate active fear expression. Here, we use in vivo fiber photometry to show that ELA results in sex-specific changes in the activity of CeAL CRF+ neurons, yielding divergent mechanisms underlying the augmented startle in ELA mice, a translationally relevant behavior indicative of heightened threat reactivity and hypervigilance. Further, chemogenic inhibition of CeAL CRF+ neurons selectively diminishes startle and produces a long-lasting suppression of threat reactivity. These findings identify a mechanism for sex-differences in susceptibility for anxiety following ELA and have broad implications for understanding the neural circuitry that encodes and gates the behavioral expression of fear.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49828-3
    DOI: 10.1038/s41467-024-49828-3
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