Uncovering the Connectivity Logic of the Ventral Tegmental Area.
Uncovering the Connectivity Logic of the Ventral Tegmental Area.
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DOI：
10.3389/fncir.2021.799688
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发表时间：
2021
影响因子：
3.5
通讯作者：
Beier KT
中科院分区：
文献类型：
--
作者：
Derdeyn P;Hui M;Macchia D;Beier KT
几十年的研究揭示了中脑多巴胺(DA)系统的显著复杂性，该系统由主要位于腹侧被盖区(VTA)和黑质致密部(SNC)的细胞组成。中脑DA系统既不是同质的，也不是服务于单一功能的，而是由不同的细胞群组成，这些细胞群(1)接受不同的输入集，(2)投射到分开的前脑部位，(3)以独特的转录和生理信号为特征。为了理解这些差异与回路功能的关系，我们首先需要了解独特的DA通路的解剖连接，以及这种连接如何与DA依赖的动机行为相关。我们和其他人提供了中脑DA细胞几个亚群的输入-输出关系的详细地图，并探索了这些不同的细胞群在指导行为输出中的作用。在这项研究中，我们将VTA输入和输出作为高维数据集(10个输出，22个输入)进行分析，采用适合于在此类数据中找到可解释模式的计算技术。除了巩固我们之前的结论，即VTA中的连通性依赖于空间组织，我们的分析还发现了一组提升到每个投影定义的VTADA单元类型的输入。例如，VTADA→Naclat细胞优先接受来自基底神经节输入的神经支配，而VTADA→杏仁核细胞优先接受来自通过VTA发送分布式输入的人群的输入，这些区域恰好是与大脑的应激回路相关的区域。此外，VTADA→NAcMed细胞接受来自视前区、腹侧苍白球和背侧被盖的腹内侧偏向输入，而VTADA→mPFC细胞则由缰核和中缝背侧的主要输入决定。我们还进一步证明，VTADA细胞的有偏输入逻辑可以使用腹侧中脑的投影结构来重现，这强化了我们的发现，即使用基于狂犬病的(RABV)电路映射识别的大多数输入差异反映了VTA内的投影原型。
Decades of research have revealed the remarkable complexity of the midbrain dopamine (DA) system, which comprises cells principally located in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Neither homogenous nor serving a singular function, the midbrain DA system is instead composed of distinct cell populations that (1) receive different sets of inputs, (2) project to separate forebrain sites, and (3) are characterized by unique transcriptional and physiological signatures. To appreciate how these differences relate to circuit function, we first need to understand the anatomical connectivity of unique DA pathways and how this connectivity relates to DA-dependent motivated behavior. We and others have provided detailed maps of the input-output relationships of several subpopulations of midbrain DA cells and explored the roles of these different cell populations in directing behavioral output. In this study, we analyze VTA inputs and outputs as a high dimensional dataset (10 outputs, 22 inputs), deploying computational techniques well-suited to finding interpretable patterns in such data. In addition to reinforcing our previous conclusion that the connectivity in the VTA is dependent on spatial organization, our analysis also uncovered a set of inputs elevated onto each projection-defined VTADA cell type. For example, VTADA→NAcLat cells receive preferential innervation from inputs in the basal ganglia, while VTADA→Amygdala cells preferentially receive inputs from populations sending a distributed input across the VTA, which happen to be regions associated with the brain’s stress circuitry. In addition, VTADA→NAcMed cells receive ventromedially biased inputs including from the preoptic area, ventral pallidum, and laterodorsal tegmentum, while VTADA→mPFC cells are defined by dominant inputs from the habenula and dorsal raphe. We also go on to show that the biased input logic to the VTADA cells can be recapitulated using projection architecture in the ventral midbrain, reinforcing our finding that most input differences identified using rabies-based (RABV) circuit mapping reflect projection archetypes within the VTA.
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影响因子：
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作者：
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