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<p>The ventral tegmental area (VTA) dopamine neurons have been implicated in diverse behaviors. These VTA<sup>dopamine</sup> neurons are intermixed with neurons that co-transmit glutamate and GABA (VTA<sup>glutamate-GABA</sup>), transmit glutamate (VTA<sup>glutamate-only</sup>) or GABA (VTA<sup>GABA-only</sup>). In dual recombinase <i>vglut2-Cre/vgat-Flp</i> transgenic mice, we combined quantitative ultrastructural analysis with 3D correlative light and electron microscopy and found that VTA<sup>glutamate-only</sup> neurons frequently established synapses on VTA<sup>dopamine</sup> and VTA<sup>glutamate-only</sup> neurons, and that VTA<sup>GABA-only</sup> neurons mostly synapsed on VTA<sup>dopamine</sup> neurons. By selective targeting of VTA subpopulations of neurons, we demonstrated that activation of VTA<sup>glutamate-only</sup> neurons is rewarding and decreases feeding behavior, while activation of VTA<sup>GABA-only</sup> neurons is aversive. We found that activation of VTA<sup>glutamate-only</sup> or VTA<sup>GABA-only</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月26日

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

摘要

The ventral tegmental area (VTA) dopamine neurons have been implicated in diverse behaviors. These VTAdopamine neurons are intermixed with neurons that co-transmit glutamate and GABA (VTAglutamate-GABA), transmit glutamate (VTAglutamate-only) or GABA (VTAGABA-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 VTAglutamate-only neurons frequently established synapses on VTAdopamine and VTAglutamate-only neurons, and that VTAGABA-only neurons mostly synapsed on VTAdopamine neurons. By selective targeting of VTA subpopulations of neurons, we demonstrated that activation of VTAglutamate-only neurons is rewarding and decreases feeding behavior, while activation of VTAGABA-only neurons is aversive. We found that activation of VTAglutamate-only or VTAGABA-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.