Input-specific control of reward and aversion in the ventral tegmental area

Ventral tegmental area (VTA) dopamine neurons play important roles in adaptive and pathological brain functions related to reward and motivation. It is unknown, however, if subpopulations of VTA dopamine neurons participate in distinct circuits that encode different motivational signatures and whether inputs to the VTA differentially modulate such circuits. Here we show that because of differences in synaptic connectivity activation of inputs to the VTA from the laterodorsal tegmentum and the lateral habenula elicit reward and aversion in mice, respectively. Laterodorsal tegmentum neurons preferentially synapse on dopamine neurons projecting to nucleus accumbens lateral shell while lateral habenula neurons synapse primarily on dopamine neurons projecting to medial prefrontal cortex as well as on GABAergic neurons in the VTA tail. These results establish that distinct VTA circuits generate reward and aversion and thereby provide a novel framework for understanding the circuit basis of adaptive and pathological motivated behaviors.