2020 Theses Doctoral

The Neural Basis of Sugar Preference

Sisti, Alexander Charles

The taste of sugar is one of the most basic sensory percepts for humans and other animals. Remarkably, animals can develop a strong preference for sugar even if lacking a functional sweet taste receptor, pointing to a detection mechanism independent of the sense of taste. Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the brainstem are activated via the gut-brain axis to create preference for sugar. These neurons are stimulated in response to sugar, but not to artificial sweeteners, and are activated by direct delivery of sugar into the gut. We demonstrate that these cells receive direct vagal inputs, which are necessary for their response to sugar. Using functional imaging we monitored the activity of the gut-brain axis, and identified the vagal neurons activated by intestinal delivery of glucose. We characterized the nature of their responses, establish their specificity, and identify the mechanism required for sugar sensation. Finally, we engineered animals where synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of a behavioral preference for sugar. Together, these findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. In addition, they explain the neural basis for the behavioral differences of sweeteners versus sugar, and uncover an essential circuit underlying sugar’s highly appetitive effects.