Modified viral-genetic mapping reveals local and global connectivity relationships of ventral tegmental area dopamine cells.
Modified viral-genetic mapping reveals local and global connectivity relationships of ventral tegmental area dopamine cells.
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DOI：
10.7554/elife.76886
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发表时间：
2022-05-23
期刊：
影响因子：
7.7
通讯作者：
Beier, Kevin
中科院分区：
文献类型：
--
作者：
Beier, Kevin
腹侧被盖区（VTADA）的多巴胺细胞对各种动机行为至关重要。这些细胞接受来自100多个解剖学上定义的大脑区域的突触输入，这使得从整个大脑的分布式输入集进行控制成为可能。基于神经化学表型和输出位点，已经做出了广泛的努力来映射VTA细胞的输入。然而，所有这些研究都有相同的基本限制，即由于enva假型病毒的非cre依赖性摄取，不能正确评估VTA局部输入。因此，局部输入对VTA的定量贡献，包括GABAergic、DAergic和5 -羟色胺ergic，尚不清楚。在这里，我使用了一种改进的病毒遗传策略，可以检查小鼠VTADA细胞的局部和远程输入。我发现近一半的VTADA细胞的总输入位于本地，揭示了之前分析中遗漏的大量输入。对VTADA细胞的抑制主要来自网状黑质，VTA和致密黑质贡献较大。除了接受VTAGABA神经元的输入外，DA神经元还与VTA内的其他DA神经元以及附近的轮辐后野相连接。最后，我表明VTADA神经元接受分布在中脑和后脑的血清素能神经元的输入，其中大部分来自中脑背。我的研究强调了使用病毒遗传试剂的适当组合来揭示大脑中特定细胞连接关系的复杂性的重要性。
Dopamine cells in the ventral tegmental area (VTADA) are critical for a variety of motivated behaviors. These cells receive synaptic inputs from over 100 anatomically defined brain regions, which enables control from a distributed set of inputs across the brain. Extensive efforts have been made to map inputs to VTA cells based on neurochemical phenotype and output site. However, all of these studies have the same fundamental limitation that inputs local to the VTA cannot be properly assessed due to non-Cre-dependent uptake of EnvA-pseudotyped virus. Therefore, the quantitative contribution of local inputs to the VTA, including GABAergic, DAergic, and serotonergic, is not known. Here, I used a modified viral-genetic strategy that enables examination of both local and long-range inputs to VTADA cells in mice. I found that nearly half of the total inputs to VTADA cells are located locally, revealing a substantial portion of inputs that have been missed by previous analyses. The majority of inhibition to VTADA cells arises from the substantia nigra pars reticulata, with large contributions from the VTA and the substantia nigra pars compacta. In addition to receiving inputs from VTAGABA neurons, DA neurons are connected with other DA neurons within the VTA as well as the nearby retrorubal field. Lastly, I show that VTADA neurons receive inputs from distributed serotonergic neurons throughout the midbrain and hindbrain, with the majority arising from the dorsal raphe. My study highlights the importance of using the appropriate combination of viral-genetic reagents to unmask the complexity of connectivity relationships to defined cells in the brain.