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

Camila Demaestri, Margaux Pisciotta, Naira Altunkeser, Georgia Berry, Hannah Hyland, Jocelyn Breton, Anna Darling, Brenna Williams and Kevin G. Bath ()
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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
Anna Darling: Columbia University
Brenna Williams: Columbia University
Kevin G. Bath: New York State Psychiatric Institute

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49828-3

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