Control of fear by discrete prefrontal GABAergic populations encoding valence-specific information

Neurons activated by learning have been ascribed the unique potential to encode memory, but the functional contribution of discrete cell types remains poorly understood. In particular, it is unclear whether learning engages specific GABAergic interneurons and, if so, whether they differ functionally from interneurons recruited by other experiences. Here, we show that fear conditioning activates a heterogeneous neuronal population in the medial prefrontal cortex (mPFC) that is largely comprised of somatostatin-expressing interneurons (SST-INs). Using intersectional genetic approaches, we demonstrate that fear-learning-activated SST-INs exhibit distinct circuit properties and are selectively reactivated to mediate cue-evoked memory expression. In contrast, an orthogonal population of SST-INs activated by morphine experience exerts opposing control over fear and supports reward-like motivational effects. These results outline an important role for discrete subsets of GABAergic cells in emotional learning and point to an unappreciated capacity for functional specialization among SST-INs.