Ventral pallidum neurons are necessary to generalize and express fear-related responding in a minimal threat setting.

Abstract

Fear generalization is a hallmark of anxiety disorders. Experimentally, fear generalization can be difficult to dissociate from its counterpart, fear discrimination. Here we use minimal threat learning procedures to reveal such a dissociation. We show that in Long Evans rats, an auditory threat cue predicting foot shock on 10% of trials produces a discriminated fear response that does not generalize to a neutral auditory cue. Even slightly higher foot shock probabilities (30% and 20%) produce fear generalization. AAV-mediated, caspase-3 deletion of ventral pallidum neurons abolishes fear generalization and reduces threat cue responding during extinction. The ventral pallidum's contribution to fear generalization and extinction threat responding does not depend on inputs from the nucleus accumbens. The results demonstrate a minimal threat learning approach to dissociate fear discrimination from fear generalization, and a novel role for the ventral pallidum in generalizing and expressing fear.Significance Statement In the laboratory, healthy mice, rats, and people generalize fear responding to a neutral cue before showing fear discrimination. However, in the real world, fear generalization is not nearly as ubiquitous in healthy individuals. Here we show that in rats, minimal threat learning procedures manipulating foot shock probability identify a boundary at which fear discrimination proceeds in the absence of fear generalization. We exploit this boundary to reveal a novel and essential role for the ventral pallidum in fear generalization.