Ventral pallidum GABA and glutamate neurons drive approach and avoidance through distinct modulation of VTA cell types

ABSTRACT The ventral pallidum (VP) contains GABA and glutamate (Glut) neurons projecting to ventral tegmental area (VTA) whose stimulation drives approach and avoidance, respectively. Yet little is known about the cell-type-specific mechanisms by which VP projections to VTA drive behavior. Here, we found that both VP GABA and Glut neurons were activated during approach to reward or delivery of an aversive stimulus. Stimulation of VP GABA neurons inhibited VTA GABA, but activated dopamine (DA) and glutamate neurons. Remarkably, this cell-type-specific recruitment was behavior-contingent such that VTA recruitment was inhibited when evoked by the subject’s own action. Conversely, VP Glut neurons activated VTA GABA, as well as DA and Glut neurons, despite driving aversion. However, VP Glut neurons evoked DA in reward-associated ventromedial nucleus accumbens (NAc), but reduced DA in aversion-associated dorsomedial NAc. These findings show how heterogeneous VP cell types can engage VTA cell types to shape approach and avoidance behaviors. HIGHLIGHTS VP GABA and Glut neurons are activated by approach to reward and aversive stimuli VP GABA and Glut neurons oppositely affect VTA GABA, both activate VTA DA and Glut VP Glut neurons activate DA release in ventral NAc but inhibit DA from dorsal NAc VTA DA responses to VP GABA activity are inhibited by the subject’s own action