Journal Article

VTA monosynaptic connections by local glutamate and GABA neurons and their distinct roles in behavior

Liu, Bing, Shevelkin, Alexey V., Morales, Marisela, Barbano, M. Flavia, Hahn, Suyun, Wang, Huiling, Yu, Kevin J., Zhang, Shiliang, Ye, Rong, Richie, Christopher T.

2025

Overview

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. While the connectivity of VTA dopamine neurons is well studied, less is known about the connectivity of VTA glutamate and GABA neurons. Here, authors show that these neurons form local circuits to modulate reward, aversion, feeding and locomotion.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/51 / 14/1 / 14/19 / 14/28 / 14/35 / 14/63 / 631/378/1788 / 631/378/3920 / 64/60 / 9/74 / Animals / Behavior / Behavior, Animal - physiology / Dopamine / Dopaminergic Neurons - metabolism / Dopaminergic Neurons - physiology / Electron microscopy / Feeding behavior / Feeding Behavior - physiology / Food / GABAergic Neurons - metabolism / GABAergic Neurons - physiology / GABAergic Neurons - ultrastructure / gamma-Aminobutyric Acid - metabolism / Glutamic Acid - metabolism / Humanities and Social Sciences / Information processing / Locomotion / Male / Mice / Mice, Inbred C57BL / Mice, Transgenic / Microscopy / multidisciplinary / Neural networks / Neurons / Recombinase / Reinforcement / Reinstatement / Reward / Science / Science (multidisciplinary) / Subpopulations / Synapses / Synapses - metabolism / Synapses - physiology / Synapses - ultrastructure / Transgenic animals / Transgenic mice / Vectors (Biology) / Ventral Tegmental Area - cytology / Ventral Tegmental Area - metabolism / Ventral Tegmental Area - physiology / Ventral tegmentum / Vesicular Glutamate Transport Protein 2 - genetics / Vesicular Glutamate Transport Protein 2 - metabolism / γ-Aminobutyric acid