Although innervation from VTA GABA neurons to the Sn is sparse compared to innervation in the VTA (Figure 1), functional activation of these fibers in the Sn may still induce behaviorally relevant effects, such as the decreased movement velocity that we observed time locked to the optical stimulation (Figure S2). Thus, while it is important to consider that the effects on consummatory behavior might also be movement-related, we observed no similar reductions in anticipatory licking. It is important

to note that DAergic projections from the Sn to the DLS are thought Wnt inhibitor to also contribute to reward consummatory behavior because the depletion of nigrostriatal DA decreases consummatory behavior (Cousins et al., 1993, Salamone et al.,

1993, Salamone et al., 1990 and Ungerstedt, 1971). Furthermore, restoring dorsal striatal DA signaling promotes feeding in aphagic DA-deficient mice (Szczypka et al., 2001). On the other hand, selectively decreasing NAc DA signaling, through specific neuronal depletion (Cousins et al., 1993 and Salamone et al., 2001) or by local action of D1 or D2 antagonists (Ikemoto and Panksepp, 1996 and Nowend et al., 2001), decreases motivation for earning food rewards but not actual consumption. Wnt assay Taken together, these data suggest that movement, motivation, and reward consumption are interdependent processes that all require DA signaling in striatal subregions. Interestingly, the cessation of reward consumption occurred only when VTA GABA neurons were directly activated. Although the NAc and its afferents clearly play important roles in mediating motivated behavioral responding (Kelley, 2004 and Stuber et al., 2011), it seems that reward consumption per se cannot be altered by the activation of VTA GABA inputs to the NAc alone. Here, we chose to investigate

the VTA GABAergic projection to about the NAc because the NAc contained the largest amount of VTA GABA fibers in the striatum and has been widely implicated in appetitive behavior (Hanlon et al., 2004, Kelley, 2004 and Krause et al., 2010). Although our results suggest that activation of VTA GABAergic inputs to the NAc alone does not reduce reward consumption, this does not rule out the possibility that other VTA GABAergic projections, such as those to the medial prefrontal cortex, may play a role in modulating reward seeking. Furthermore, although we show that activation of VTA GABA neurons directly alters the activity of neighboring VTA DA neurons, as well as the release of DA in the NAc, we cannot rule out that the activation of VTA GABA neurons results in additional changes in DA signaling in other forebrain target regions, other than the NAc, that could also play a role in the cessation of reward consumption. Although VTA GABA activation disrupts reward consumption, activation of these neurons can also cause a conditioned place aversion (Tan et al., 2012 [linked paper, this issue of Neuron]).