Figure 1.

Inhibitory effects originating from the lateral habenula (LHb) create functional heterogeneity among dopamine (DA) neurons. LHb neurons encode negative motivational values (inhibited by reward and excited by punishment) and inhibit DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) through the rostromedial tegmental nucleus (RMTg). In the monkey the LHb-induced inhibition is stronger for DA neurons in the medial part of SNc. The medial DA neurons thus signal positive values, and thereby facilitate reward-approaching actions (shown in red) when reward is predicted and suppress actions (blue) when punishment is predicted. In contrast, the lateral DA neurons are excited when either reward or punishment is predicted, and thereby facilitate both reward-approaching actions when reward is predicted (red) and punishment-avoiding actions when punishment is predicted (blue). R and P indicate reward and punishment. The punishment-related excitation of the lateral DA neurons may be caused by inputs from other brain areas sensitive to alert signals. Note that this scheme may not apply to all DA neurons; for example, some DA neurons in the rodent VTA receive excitatory inputs from the LHb (see text for details).