Ensemble encoding of conditioned fear by prefrontal somatostatin interneurons

Neurons preferentially activated by learning have been ascribed the unique potential to encode memory. However, it remains unclear which genetically-defined cell types are recruited as part of such an ensemble, or what role discrete subpopulations play in behavior. Here we show that fear conditioning activates a heterogeneous neural ensemble in the medial prefrontal cortex (mPFC), comprised to a large degree of GABAergic interneurons immunoreactive for somatostatin (SST-INs). Using an intersectional genetic approach, we demonstrate that fear learning-activated SST-INs exhibit distinct circuit properties, are preferentially reactivated during memory retrieval, and mediate the expression of defensive freezing. We further show that a rewarding experience, morphine treatment, activates an orthogonal SST-IN population that exerts opposing control over fear. These results outline an important role for discrete GABAergic ensembles in fear memory encoding, and point to an unappreciated capacity for functional specialization among SST-INs. ### Competing Interest Statement P.J.K. is co-founder and shareholder in Eolas Therapeutics Inc., which has a licensing agreement with AstraZeneca to develop a novel therapeutic for the treatment of substance use disorders.