Barbano M Flavia, Wang Huiling, Zhang Shiliang, Shevelkin Alexey V, Yu Kevin J, Richie Christopher T, Liu Bing, Hahn Suyun, Ye Rong, Morales Marisela
Integrative Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Confocal and Electron Microscopy Core, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Nat Commun. 2025 Sep 26;16(1):8500. doi: 10.1038/s41467-025-63396-0.
The ventral tegmental area (VTA) dopamine neurons have been implicated in diverse behaviors. These VTA neurons are intermixed with neurons that co-transmit glutamate and GABA (VTA), transmit glutamate (VTA) or GABA (VTA). 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 neurons frequently established synapses on VTA and VTA neurons, and that VTA neurons mostly synapsed on VTA neurons. By selective targeting of VTA subpopulations of neurons, we demonstrated that activation of VTA neurons is rewarding and decreases feeding behavior, while activation of VTA neurons is aversive. We found that activation of VTA or VTA 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.
腹侧被盖区(VTA)多巴胺能神经元与多种行为有关。这些VTA神经元与共同释放谷氨酸和γ-氨基丁酸(VTA)、释放谷氨酸(VTA)或γ-氨基丁酸(VTA)的神经元相互混合。在双重组酶vglut2-Cre/vgat-Flp转基因小鼠中,我们将定量超微结构分析与三维相关光镜和电镜相结合,发现VTA神经元经常在VTA和VTA神经元上建立突触,并且VTA神经元大多与VTA神经元形成突触。通过选择性靶向VTA神经元亚群,我们证明激活VTA神经元是有奖励作用的,并会减少进食行为,而激活VTA神经元则是厌恶的。我们发现激活VTA或VTA神经元会对学习获取食物奖励产生负面影响,并损害线索诱导的觅食行为恢复。总的来说,我们证明了一个意想不到的VTA微回路的单突触特性,其中不同的神经元成分整合了与奖励、厌恶和进食相关的信息。