VTA monosynaptic connections by local glutamate and GABA neurons and their distinct roles in behavior
- M. Flavia Barbano
- Huiling Wang
- Shiliang Zhang
- Alexey V. Shevelkin
- Kevin J. Yu
- Christopher T. Richie
- Bing Liu
- Suyun Hahn
- Rong Ye
- Marisela Morales
2025-09-26
The ventral tegmental area (VTA) dopamine neurons have been implicated in diverse behaviors. These VTA dopamine neurons are intermixed with neurons that co-transmit glutamate and GABA (VTA glutamate-GABA ), transmit glutamate (VTA glutamate-only ) or GABA (VTA GABA-only ). In dual recombinase vglut2-Cre/vgat-Flp transgenic mice, we combined quantitative ultrastructural analysis with 3D correlative light and electron microscopy and found that VTA glutamate-only neurons frequently established synapses on VTA dopamine and VTA glutamate-only neurons, and that VTA GABA-only neurons mostly synapsed on VTA dopamine neurons. By selective targeting of VTA subpopulations of neurons, we demonstrated that activation of VTA glutamate-only neurons is rewarding and decreases feeding behavior, while activation of VTA GABA-only neurons is aversive. We found that activation of VTA glutamate-only or VTA GABA-only neurons negatively affected learning to obtain food reward, and impaired cue-induced reinstatement of food-seeking behavior. Collectively, we demonstrated the monosynaptic properties of an unexpected VTA microcircuitry in which distinct neuronal components integrate information related to reward, aversion, and feeding.