Dietary sugar inhibits satiation by decreasing the central processing of sweet taste

From humans to flies, exposure to diets rich in sugar and fat lowers taste sensation, changes food choices, and promotes feeding. However, how exactly these peripheral alterations influence eating is unknown. Here we used the genetically tractable organism D. melanogaster to define the neural mechanisms through which this occurs. We identified a small population of protocerebral anterior medial dopaminergic neurons (PAM DANs) that innervates the β′2 compartment of the mushroom body and responds to sweet taste. In animals fed a high sugar diet, the response of PAM-β′2 to sweet stimuli was reduced and delayed, and sensitive to the strength of the sweet signal transmission out of the sensory neurons. We show that PAM-β′2 DANs activity controls feeding rate and satiation. Specifically, closed-loop optogenetic activation of β′2 DANs rescued satiation and restored normal eating in animals fed high sucrose. These data support the hypothesis that sensory signals modulate meal size and feeding − a process known as sensory-enhanced satiation − and define specific DANs as the neural basis for this behavior. Further, our results suggest that diet-dependent alterations in taste sensation weaken sensory-enhanced satiation by impairing the central dopaminergic processing of sweet sensory signals.