Long-range projection neurons of the mouse ventral tegmental area: a single-cell axon tracing analysis
Long-range projection neurons of the mouse ventral tegmental area: a single-cell axon tracing analysis
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DOI：
10.3389/fnana.7015.00059
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发表时间：
2015-05-19
影响因子：
2.9
通讯作者：
Prensa, Lucia
中科院分区：
文献类型：
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作者：
Aransay, Ana;Rodriguez-Lopez, Claudia;Prensa, Lucia
腹侧被盖区（VIA）产生的通路在期望和实现奖励的过程中释放多巴胺和其他神经递质，并被认为是大脑网络的中心环节，创造驱动力，快乐和成瘾。虽然VIA投射的全球模式是众所周知的，但单个VIA神经元的实际轴突布线从未被研究过。在这里，我们标记和分析了30个VIA单神经元的轴突，通过单细胞转染与Sindbis-pal-eGFP载体在小鼠中。这些观察结果与通过用生物素化葡聚糖胺的离子电泳微沉积物标记小群体VIA细胞的轴突获得的观察结果进行了补充。在单细胞标记实验中，从连续切片重建每个完整的轴突树，通过体视学估计末端轴突乔木的长度，并通过酪氨酸羟化酶免疫荧光双标记测试多巴胺能表型。我们观察到两个主要的，明显不同的VIA细胞形态：神经元与一个主要的轴突只针对前脑结构（FPN细胞），和神经元与多分支轴突靶向前脑和脑干（F + BSPN细胞）。多巴胺能表型在FPN细胞中观察到。此外，基于其投射靶点，可以在FPN细胞中区分出四种“亚型”：（1）“中皮质边缘”FPN，其投射到新皮质和基底前脑两者;（2）“中皮质”FPN，其几乎专门支配新皮质;（3）“中皮质边缘”FPN，其投射到基底前脑、中脑和尾壳核;以及（4）“中纹状体”FPN，其仅靶向尾壳核。F + BSPN细胞散在分布于VIA内，而中脑边缘核神经元则分布于黑质旁核内。所观察到的布线结构的多样性与不同的VIA细胞亚群调节前脑和脑干结构的特定集合的活性的概念一致。
Pathways arising from the ventral tegmental area (VIA) release dopamine and other neurotransmitters during the expectation and achievement of reward, and are regarded as central links of the brain networks that create drive, pleasure, and addiction. While the global pattern of VIA projections is well-known, the actual axonal wiring of individual VIA neurons had never been investigated. Here, we labeled and analyzed the axons of 30 VIA single neurons by means of single-cell transfection with the Sindbis-pal-eGFP vector in mice. These observations were complemented with those obtained by labeling the axons of small populations of VIA cells with iontophoretic microdeposits of biotinylated dextran amine. In the single-cell labeling experiments, each entire axonal tree was reconstructed from serial sections, the length of terminal axonal arbors was estimated by stereology, and the dopaminergic phenotype was tested by double-labeling for tyrosine hydroxylase immunofluorescence. We observed two main, markedly different VIA cell morphologies: neurons with a single main axon targeting only forebrain structures (FPN cells), and neurons with multibranched axons targeting both the forebrain and the brainstem (F + BSPN cells). Dopaminergic phenotype was observed in FPN cells. Moreover, four "subtypes" could be distinguished among the FPN cells based on their projection targets: (1) "Mesocorticolimbic" FPN projecting to both neocortex and basal forebrain; (2) "Mesocortical" FPN innervating the neocortex almost exclusively; (3) "Mesolimbic" FPN projecting to the basal forebrain, accumbens and caudateputamen; and (4) "Mesostriatal" FPN targeting only the caudateputamen. While the F + BSPN cells were scattered within VIA, the mesolimbic neurons were abundant in the paranigral nucleus. The observed diversity in wiring architectures is consistent with the notion that different VIA cell subpopulations modulate the activity of specific sets of prosencephalic and brainstem structures.