Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical UniversityXi'an, China.
College of Life Sciences and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan UniversityYanan, China.
Front Neural Circuits. 2017 Aug 17;11:57. doi: 10.3389/fncir.2017.00057. eCollection 2017.
As the main input nucleus of the basal ganglion, the striatum executes different functions, including motivation, reward and attention. The functions of the striatum highly rely on its subregions that receive projections from various cortical areas and the distribution of striatonigral neurons that express D1 dopamine (DA) receptors (or D1 medium-sized spiny neurons, D1 MSNs) and striatopallidal neurons that express D2 DA receptors (or D2 MSNs). Using bacterial artificial chromosome (BAC) transgenic mice, several studies have recently been performed on the spatial distribution of D1 and D2 MSNs. However, these studies mainly focused on enumeration of either D1-enhanced fluorescent protein (eGFP) or D2-eGFP in mice. In the present work, we used Drd1a-tdTamato and Drd2-eGFP double BAC transgenic mice to evaluate the spatial pattern of D1 MSNs (red fluorescence) and D2 MSNs (green fluorescence) along the rostro-caudal axis of the dorsal striatum. The dorsal striatum was divided into three subregions: rostral caudoputamen (CPr), intermediate CP (CPi), and caudal CP (CPc) across the rostral-caudal extent of the striatum. The results demonstrate that D1 and D2 MSNs were intermingled with each other in most of these regions. The cell density of D1 MSNs was slightly higher than D2 MSNs through CPr, CPi, and CPc, though it did not reach significance. However, in CPi, the ratio of D1/D2 in the ventromedial CPi group was significantly higher than those in dorsolateral, dorsomedial, and ventrolateral CPi. There was similar proportion of cells that co-expressed D1 and D2 receptors. Moreover, we demonstrated a pathway-specific activation pattern of D1 MSNs and D2 MSNs in a manic like mouse model induced by D-Amphetamine by utilizing this double transgenic mice and c-fos immunoreactivity. Our results may provide a morphological basis for the function or pathophysiology of striatonigral and striatopallidal neurons with diverse cortical inputs to the dorsal striatum.
作为基底神经节的主要输入核，纹状体执行着不同的功能，包括动机、奖励和注意力。纹状体的功能高度依赖于其接收来自各种皮质区域投射的亚区，以及表达 D1 多巴胺（DA）受体（或 D1 中型棘突神经元，D1 MSNs）的纹状体苍白球神经元和表达 D2 DA 受体（或 D2 MSNs）的分布。使用细菌人工染色体（BAC）转基因小鼠，最近有几项研究针对 D1 和 D2 MSNs 的空间分布进行了研究。然而，这些研究主要集中在对 D1 增强型荧光蛋白（eGFP）或 D2-eGFP 的计数上。在本工作中，我们使用 Drd1a-tdTamato 和 Drd2-eGFP 双 BAC 转基因小鼠来评估 D1 MSNs（红色荧光）和 D2 MSNs（绿色荧光）在背侧纹状体的头尾轴上的空间模式。背侧纹状体被分为三个亚区：前尾苍白球（CPr）、中间 CP（CPi）和尾苍白球（CPc），横跨纹状体的头尾范围。结果表明，在这些区域的大部分区域，D1 和 D2 MSNs 相互交织。在 CPr、CPi 和 CPc 中，D1 MSNs 的细胞密度略高于 D2 MSNs，但没有达到显著水平。然而，在 CPi 中，腹内侧 CPi 组的 D1/D2 比值明显高于背外侧、背内侧和腹外侧 CPi。表达 D1 和 D2 受体的细胞比例相似。此外，我们利用这种双转基因小鼠和 c-fos 免疫反应性，在 D-安非他命诱导的躁狂样小鼠模型中，展示了 D1 MSNs 和 D2 MSNs 的特定通路激活模式。我们的结果可能为具有不同皮质输入的背侧纹状体的纹状体苍白球和纹状体黑质神经元的功能或病理生理学提供形态学基础。
