Zona Incerta activity dynamics underlying associative fear learning and fear generalization

Recent studies suggest that the Zona Incerta (ZI) plays a role in fear learning and recall. However, there is a clear gap in knowledge as to whether the ZI can encode fear evoking threats and cues that predict them. Here, we subject mice to a classical fear conditioning paradigm while recording the in-vivo calcium dynamics of ZI neurons. We observed that ZI neurons can encode not only a fear evoking stimulus, but can also learn to encode predictive cues, associate them with the unconditioned fear evoking stimulus, and discriminate them from neutral non-predictive cues. While the ZI across all mice learned to become mainly excited by fear predictive cues, only mice that did not generalize fear became largely inhibited by non-predictive cues and better discriminated the two. Together, we provide extensive evidence that the ZI differentially encode fear predictive and non-predictive cues in a generalization dependent manner.