ANTAGONISTIC CODING OF ENERGY INTAKE AND ENERGY EXPENDITURE BY VTA DOPAMINE SUBPOPULATIONS

Animals must continuously balance energy intake and expenditure to maintain metabolic homeostasis. Feeding provides energy, whereas locomotion represents a major energetic cost, yet how the brain coordinates these opposing motivated behaviors remains unknown. VTA dopamine (VTA-DA) neurons regulate motivated behaviors and encode reward and reward-related variables heterogeneously. However, it remains unclear how VTA-DA neurons integrate these competing behaviors. Additionally, it is unknown how motivational state changes, such as hunger or enhanced exercise drive, influence these responses. The aim of this study was therefore to uncover how individual VTA-DA neurons encode these competing rewards, and how motivational state affects their function.
We performed 1-photon calcium imaging in DAT-cre mice expressing GCaMP6m in the VTA, while they freely explored an arena with multiple rewards, including food, water and a running wheel. To study the effects of increased drive for feeding and voluntary exercise, calcium activity of single neurons was recorded during food restriction and after repeated running wheel exposure. To assess the contribution of anatomically different subpopulations on food intake and locomotion, we recorded and optogenetically activated projection-specific VTA-DA neurons.
We found that VTA-DA neurons encode food and voluntary exercise in an opposite manner, but not food and water. Similarly, projections to different targets controlled feeding and locomotion antagonistically. During food restriction and enhanced exercise drive, the responses of VTA-DA neurons became tuned to the prioritized reward. These results suggest that VTA-DA neuron subpopulations distinguish between behaviors leading to energy intake and expenditure, and shift their responses according to motivational state changes.