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

Ventral tegmental area (VTA) dopamine neurons have important roles in adaptive and pathological brain functions related to reward and motivation. However, it is unknown whether 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 the nucleus accumbens lateral shell, whereas lateral habenula neurons synapse primarily on dopamine neurons projecting to the medial prefrontal cortex as well as on GABAergic (γ-aminobutyric-acid-containing) neurons in the rostromedial tegmental nucleus. These results establish that distinct VTA circuits generate reward and aversion, and thereby provide a new framework for understanding the circuit basis of adaptive and pathological motivated behaviours. Through the use of a combination of state-of-the-art techniques, different populations of ventral tegmental area dopamine neurons in the mouse are shown to form separate circuits with distinct connectivity: neurons receiving input from the laterodorsal tegmentum and lateral habenula are found to mediate reward and aversion, respectively. Dopamine neurons in the ventral tegmental area (VTA) are perhaps best known for their reward-related activity, but they can also signal aversion. Here, the authors show that different populations of VTA neurons form separate circuits with distinct connectivity for reward and aversion. Using a combination of state-of-the-art functional anatomical techniques, they find that neurons receiving input from the laterodorsal tegmentum and lateral habenula mediate reward and aversion, respectively.