Nov. 28, 2023

New research from the Witten and Peña labs at PNI explores the possibility that food and social motivations can interact at a cellular level.Animals are motivated by a combination of external and internal factors, which together promote behaviors that ensure biological, reproductive, social, and psychological needs are met. On some level, motivated behaviors can be reduced to single motivating factors (e.g. animals that are hungry will seek food). However, motivations can also interact: perhaps you are more likely to enter a pizza restaurant if you are hungry and you see your friend inside.

Researchers in the Witten lab recorded activity from populations of individual dopamine neurons in the ventral tegmental area (VTA), an area of the brain strongly implicated in driving motivated behavior, while mice were presented with either a palatable food stimulus or a social stimulus (another mouse of the same or opposite sex). Recording from the same population of cells across conditions using two-photon calcium imaging, they found that more often than expected by chance, the same dopamine cells were responsive to both food and social stimuli. In addition, hunger or social experience further increased the amount of overlap in the representations of each stimulus type. Collaboration with the Peña lab allowed for innovative single-nucleus transcriptional analysis of dopaminergic VTA cells to mirror the single-cell resolution of calcium imaging. This analysis showed that individual dopaminergic VTA cells express genes that are related to feeding and also social behavior (for example, insulin receptors and androgen receptors), consistent with overlapping food and social representations. Furthermore, cells analyzed from hungry mice had alterations in genes associated with neuronal excitability. This suggests a mechanism through which dopaminergic VTA cells in hungry mice are more likely to become activated by a distinct motivating stimulus.

These findings are important to the field because they suggest that the dopaminergic cells in the VTA encode different rewards (in this case food and social) in a so-called “common currency”. This could be useful in supporting a unified decision that involves weighting different motivations. Co-first author and former PNI doctoral student Lindsay Willmore explains, “while a lot of classical work has shown similarities across dopamine neurons in reward responses and more modern work has focused on heterogeneity in dopamine encoding of complex reward-predictive (conditioned) features, our study comes back to homogeneity in how unconditioned rewards (even of different types) are encoded by largely the same sets of neurons.”

The collaborative environment at PNI provided the combined expertise of researchers from the Witten and Peña labs, which was critical for the completion of this project. Addie Minerva, a co-first author and current PNI doctoral student, points out that “the final results really would not have been achieved without the diversity of perspectives that we were able to achieve through collaboration at PNI.”