Excessive sugar consumption is thought to contribute to the current obesity and diabetes epidemics. We think of sugar as sweet and hence appetitive. Yet, sugar consumption is highly rewarding even in the absence of sweet taste, as animals lacking sweet taste receptors still prefer sugar solutions. What is the neural basis for the mammalian preference for sugar? Using a novel research platform that combines behavioral, optogenetic, pharmacologic and genetic tools, we have identified a nucleus in the brainstem that is activated by sugar, but not by artificial sweetener, and is necessary for taste-independent preference for sugar. I hypothesize that this brainstem nucleus is the nexus of a dedicated neuronal circuit that mediates preference to sugar and is activated by glucose acting in the gut independent of taste signaling. I will test this hypothesis by addressing three questions: (1) How do natural sugars activate this brainstem circuit? (2) Does this sugar-responsive nucleus drive preference formation? (3) What are the direct inputs and outputs of the sugar-responsive neurons? Answering these three questions will establish the role of this brainstem nucleus in mediating sugar-preference behaviors, and will provide a foundation for further investigation into the mechanisms supporting sugar preference. Beyond answering these basic scientific questions, elucidating the mammalian sugar-preference circuit will have important health implications: by enhancing our understanding of how obesity and diabetes develops, we open the possibility of finding new prevention and treatment approaches.