Ventral Pallidum Neurons Are Necessary to Generalize and Express Fear-Related Responding in a Minimal Threat Setting

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 footshock on 10% of trials produces a discriminated fear response that does not generalize to a neutral auditory cue. In contrast, even slightly higher footshock 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.