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

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  • M. Flavia Barbano

    (National Institutes of Health)

  • Huiling Wang

    (National Institutes of Health)

  • Shiliang Zhang

    (National Institutes of Health)

  • Alexey V. Shevelkin

    (National Institutes of Health)

  • Kevin J. Yu

    (National Institutes of Health)

  • Christopher T. Richie

    (National Institutes of Health)

  • Bing Liu

    (National Institutes of Health)

  • Suyun Hahn

    (National Institutes of Health)

  • Rong Ye

    (National Institutes of Health)

  • Marisela Morales

    (National Institutes of Health)

Abstract

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.

Suggested Citation

  • 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. "VTA monosynaptic connections by local glutamate and GABA neurons and their distinct roles in behavior," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63396-0
    DOI: 10.1038/s41467-025-63396-0
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    References listed on IDEAS

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    1. Ji Hoon Yoo & Vivien Zell & Navarre Gutierrez-Reed & Johnathan Wu & Reed Ressler & Mohammad Ali Shenasa & Alexander B. Johnson & Kathryn H. Fife & Lauren Faget & Thomas S. Hnasko, 2016. "Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    2. M. Flavia Barbano & Shiliang Zhang & Emma Chen & Orlando Espinoza & Uzma Mohammad & Yocasta Alvarez-Bagnarol & Bing Liu & Suyun Hahn & Marisela Morales, 2024. "Lateral hypothalamic glutamatergic inputs to VTA glutamatergic neurons mediate prioritization of innate defensive behavior over feeding," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
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