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Anatomic resolution of neurotransmitter-specific projections to the VTA reveals diversity of GABAergic inputs.
Nature Neuroscience ( IF 25.0 ) Pub Date : 2020-06-15 , DOI: 10.1038/s41593-020-0657-z
Marta E Soden 1, 2 , Amanda S Chung 1, 2 , Beatriz Cuevas 2 , Jesse M Resnick 1 , Rajeshwar Awatramani 3 , Larry S Zweifel 1, 2
Affiliation  

The ventral tegmental area (VTA) is important for reward processing and motivation. The anatomic organization of neurotransmitter-specific inputs to the VTA remains poorly resolved. In the present study, we mapped the major neurotransmitter projections to the VTA through cell-type-specific retrograde and anterograde tracing. We found that glutamatergic inputs arose from a variety of sources and displayed some connectivity biases toward specific VTA cell types. The sources of GABAergic projections were more widespread, displayed a high degree of differential innervation of subregions in the VTA and were largely biased toward synaptic contact with local GABA neurons. Inactivation of GABA release from the two major sources, locally derived versus distally derived, revealed distinct roles for these projections in behavioral regulation. Optogenetic manipulation of individual distal GABAergic inputs also revealed differential behavioral effects. These results demonstrate that GABAergic projections to the VTA are a major contributor to the regulation and diversification of the structure.



中文翻译:

神经递质特异性投射到 VTA 的解剖分辨率揭示了 GABAergic 输入的多样性。

腹侧被盖区 (VTA) 对于奖励处理和动机很重要。VTA 的神经递质特定输入的解剖组织仍未得到很好的解决。在本研究中,我们通过细胞类型特异性逆行和顺行追踪将主要神经递质投射映射到 VTA。我们发现谷氨酸能输入来自多种来源,并显示出对特定 VTA 细胞类型的一些连接偏差。GABA 能投射的来源更为广泛,显示出 VTA 中子区域的高度差异神经支配,并且在很大程度上偏向于与局部 GABA 神经元的突触接触。从两个主要来源(局部来源与远端来源)释放 GABA 的失活揭示了这些预测在行为调节中的不同作用。对单个远端 GABAergic 输入的光遗传学操作也揭示了不同的行为效应。这些结果表明,对 VTA 的 GABAergic 投射是结构调节和多样化的主要贡献者。

更新日期:2020-06-15
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