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Sex differences in BNST signaling and BNST CRF in fear processing
Olivia J Hon1, Sofia Neira1, Meghan E Flanigan1
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, United States.
Elife
|December 5, 2025
Summary
This study reveals sex differences in sustained fear responses. Males show heightened bed nucleus of the stria terminalis (BNST) activity, while females rely on corticotropin-releasing factor (CRF) for fear regulation.
Area of Science:
- Neuroscience
- Behavioral Biology
- Psychology
Background:
- Fear responses are vital for survival but excessive fear can be detrimental.
- Two forms of fear exist: phasic (immediate) and sustained (prolonged, often from uncertainty).
- The bed nucleus of the stria terminalis (BNST) and corticotropin-releasing factor (CRF) signaling are implicated in fear.
Purpose of the Study:
- Investigate the neural mechanisms of phasic and sustained fear in male and female mice.
- Focus on the role of the BNST and CRF signaling in sex-specific fear responses.
- Understand how these mechanisms contribute to anxiety and trauma-related disorders.
Main Methods:
- Utilized rodent models to study fear conditioning, specifically partial fear conditioning for sustained fear.
- Measured brain activity, focusing on the BNST, in response to threat cues.
- Examined the effect of CRF knockdown on fear responses in both sexes.
Main Results:
- Sustained fear induced greater arousal and BNST activity in males, particularly with ambiguous threat cues.
- Females showed reduced BNST and BNSTCRF activity compared to males.
- CRF knockdown increased fear responses in females but not in males, indicating its crucial role in female fear regulation.
Conclusions:
- Significant sex differences exist in the neural processing of sustained fear.
- BNST and CRF signaling play distinct roles in fear responses between males and females.
- These findings may inform sex-specific treatments for anxiety and trauma-related disorders.
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