Ventral Pallidum GABA Neuron Inhibition Augments Context-Appropriate Defensive Responses to Learned Threat Cues

The ventral pallidum (VP) is embedded within the brain circuits controlling motivated behavior, which are heavily implicated in addiction and other psychiatric disorders. Prior work showed that VP GABAergic neurons (VP^GABA) promote reward approach and seeking, while intermixed populations of VP glutamate neurons instead promote avoidance and aversion. Some have thus suggested a functional dichotomy between these VP subpopulations in reward versus threat. We test this hypothesis by asking how inhibiting VP^GABA impacts active and passive defensive responses to learned threat cues. We taught GAD1:Cre rats with inhibitory VP^GABA DREADDs (or WT littermates without DREADDs) that a metal-wrapped probe delivers shock, or that a 20sec auditory cue precedes footshocks. These threats elicit active defensive burying, or passive freezing responses, respectively. We found that VP^GABA inhibition markedly increased stimulus-appropriate defensive responses to both types of threats, but failed to alter new learning about threat-suggesting VP^GABA mediates aversive motivation but not memory formation. VP^GABA inhibition also altered threat-related c-Fos expression patterns within VP cell populations, and in their efferent target region LHb-pointing to underlying circuit mechanisms of these conditioned defensive responses. Results indicate that VP^GABA neurons not only promote reward seeking as previously reported, but that they also actively inhibit defensive responses to threats that might otherwise limit reward seeking. This refines our understanding of subcortical valanced motivation circuits, and may suggest new targets for intervening in disorders like addiction and depression.