NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
Project Summary Animals learn to prefer foods that are calorie-rich. This process likely contributes to the motivational pull of energy dense foods and promotes their overconsumption in obesity, but how this learning is implemented in the brain is unknown. Dopamine (DA) is important for learning associations between cues and rewards, and we have shown that mesolimbic DA is necessary for flavor nutrient-learning. We therefore performed a screen for brain sites where nutrients trigger DA release, reasoning that this would reveal potential sites involved in learning about food. Unexpectedly, we observed little DA release in canonical striatal targets of the mesolimbic DA pathway. Instead, post-ingestive nutrients trigger DA release selectively in a small region of the anterior basolateral amygdala (BLA). Remarkably, this hotspot for nutrient-triggered DA release is localized to the left side of the brain in both mice and humans, revealing that the DA system is functionally lateralized. In Aim 1, we investigate the mechanisms by which DA drives learning about food in the left anterior BLA. In Aim 2, we explore the function of lateralized DA release in the right and left BLA through targeted manipulations. In Aim 3, we map out the circuits that enable GI nutrients to selectively trigger DA release on one side of the brain. Together, these experiments will reveal the central mechanisms by which animals learn about the nutrient content of their food. They will also reveal how internal nutrient signals are unexpectedly biased to the left hemisphere of the brain.
Up to $2.6M
2029-08-31
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