Extinction-recruited prefrontal-hypothalamic pathway encodes positive affect to sustain extinction and prevent relapse in PTSD mice

Notably, extinction involves not only fear inhibition but also affective engagement. However, whether and how internal affective components contribute to extinction retrieval and long-term persistence remain unclear.

Here, we demonstrate that positive affective experiences arising during extinction govern the long-term persistence of extinction and resistance to spontaneous recovery. We identify a subpopulation of medial prefrontal cortex (mPFC) extinction neurons projecting to supramammillary nucleus glutamatergic (SuMGlu) neurons that encodes positive affective experience during extinction and selectively governs long-term extinction persistence.