Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance

Lateral habenula (LHb) projections to the ventral midbrain, including the rostromedial tegmental nucleus (RMTg) conveys negative reward-related information, but the behavioral ramifications of selective activation of this pathway remain unexplored. We found that exposure to aversive stimuli in mice increased LHb excitatory drive onto RMTg neurons. Further, optogenetic activation of this pathway promoted active, passive, and conditioned behavioral avoidance. These data demonstrate that activity of LHb efferents to the midbrain is aversive, but can also serve to negatively reinforce behavioral responding.