The ventrolateral periaqueductal grey updates fear via positive prediction error.

Aversive, positive prediction error (+PE) provides a mechanism to update and increase future fear to uncertain threat predictors. The ventrolateral periaqueductal grey (vlPAG) has been offered as a neural locus for +PE computation. Yet, a causal demonstration of vlPAG +PE activity to update fear remains elusive. We devised a fear discrimination procedure in which a danger cue predicts shock deterministically and an uncertainty cue predicts shock probabilistically, requiring prediction errors to achieve an appropriate fear response. Recording vlPAG single-unit activity during fear discrimination in Long-Evans rats, we reveal activity related to shock is consistent with +PE and updates subsequent fear to uncertainty at the trial level. We further demonstrate that vlPAG inhibition during shock selectively decreases future fear to uncertainty, but not danger, and temporal emergence of this effect is consistent with single-unit activity. These findings provide causal evidence that vlPAG +PE is necessary for fear updating.