Untangling dopamine and glutamate in the ventral tegmental area

Prevost, E. D.; Ward, L. A.; Alas, D.; Aimale, G.; Ikenberry, S.; Fox, K.; Pelletier, J.; Ly, A.; Ball, J.; Kilpatrick, Z. P.; Price, K.; Polter, A. M.; Root, D. H.

doi:10.1101/2025.02.25.640201

bioRxiv · 10.1101/2025.02.25.640201

Untangling dopamine and glutamate in the ventral tegmental area

Prevost, E. D.·Ward, L. A.·Alas, D.·Aimale, G.·Ikenberry, S.·Fox, K.·Pelletier, J.·Ly, A.·Ball, J.·Kilpatrick, Z. P.·Price, K.·Polter, A. M.·Root, D. H.

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Abstract

Ventral tegmental area (VTA) dopamine neurons are of great interest for their central roles in motivation, learning, and psychiatric disorders. While hypotheses of VTA dopamine neuron function posit a homogenous role in behavior (e.g., prediction error), they do not account for molecular heterogeneity. We find that glutamate-dopamine, nonglutamate-dopamine, and glutamate-only neurons are dissociable in their signaling of reward and aversion-related stimuli, prediction error, and electrical properties. In addition, glutamate-dopamine and nonglutamate-dopamine neurons differ in dopamine release dynamics. Aversion-related recordings of all dopamine neurons (not considering glutamate co-transmission) showed a mixed response that obscured dopamine subpopulation function. Within glutamate-dopamine neurons, glutamate and dopamine release had dissociable contributions toward reward and aversion-based learning and performance. Based on our results, we propose a new hypothesis on VTA dopamine neuron function: that dopamine neuron signaling patterns and their roles in motivated behavior depend on whether or not they co-transmit dopamine with glutamate.

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Prevost, E. D., Ward, L. A., Alas, D., Aimale, G., Ikenberry, S., Fox, K., Pelletier, J., Ly, A., Ball, J., Kilpatrick, Z. P., Price, K., Polter, A. M., Root, D. H.. 2025-02-26. Untangling dopamine and glutamate in the ventral tegmental area. https://doi.org/10.1101/2025.02.25.640201

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