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August 6, 2026Journal of Clinical InvestigationOpen Access

Extinction-recruited prefrontal-hypothalamic pathway encodes positive affect to sustain fear extinction in post-traumatic stress mouse model

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Authors

ZLZe-Jie LinXWXinrong WuMWMing-Yang Wei

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Overview

Randomized trial investigates how positive feelings during extinction influence long-term PTSD treatment success, suggesting new therapeutic targets.

Key Points

  • The aim is to understand how positive affect during fear extinction affects long-term outcomes in PTSD.
  • Identified a specific neural pathway from mPFC to SuM Glu neurons involved in positive affect during extinction.
  • Conducted transcriptomic profiling to analyze gene expression in extinction neurons.
  • Utilized bidirectional manipulation of SIRT1 in a PTSD mouse model to assess effects on extinction relapse.
  • Positive affective experiences during extinction led to increased long-term persistence of fear extinction.
  • SIRT1 levels were found to be enriched in SuM-projecting neurons, affecting relapse vulnerability.
  • Manipulation of SIRT1 demonstrated significant changes in extinction relapse risk in the PTSD model.

Cite This Study

Lin et al. (2026) studied this question.

synapsesocial.com/papers/6a7437ba764cddc9499d5449https://doi.org/10.1172/jci206270
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