Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis.

Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis.
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DOI:
10.1038/s41598-023-27727-9
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发表时间:
2023-04-07
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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交感神经系统对于控制多种心脏功能至关重要。然而,目前尚无关于心脏交感神经支配的全面、详细的神经解剖图谱。在此,我们结合了一系列先进技术,包括组织平铺处理、针对酪氨酸羟化酶(TH,一种交感神经标志物)的免疫组织化学、共聚焦显微镜以及Neurolucida 360软件,对C57Bl/6 J小鼠全心房交感神经节后神经支配的地形分布进行追踪、数字化和定量绘图。我们发现:(1)4 - 5条主要的外在TH免疫反应阳性(TH-IR)神经束分别在上腔静脉、右心房(RA)、左前腔静脉以及左心房(LA)的肺静脉(PVs)根部进入心房。尽管这些神经束投射到心房的不同区域,但其投射区域部分重叠。(2)TH-IR轴突和终末密度在心房的不同部位差异显著,窦房结区域附近的神经支配密度最大(P < 0.05,n = 6)。(3)TH-IR轴突还支配血管和脂肪细胞。(4)心脏内在神经节中的许多主神经元和小强荧光细胞也呈强TH-IR阳性。我们的研究提供了一份全面的儿茶酚胺能传出轴突形态、神经支配以及在全心房单细胞/轴突/膨体尺度上分布的地形图谱,可用于未来创建心脏交感神经 - 脑图谱的研究。
The sympathetic nervous system is crucial for controlling multiple cardiac functions. However, a comprehensive, detailed neuroanatomical map of the sympathetic innervation of the heart is unavailable. Here, we used a combination of state-of-the-art techniques, including flat-mount tissue processing, immunohistochemistry for tyrosine hydroxylase (TH, a sympathetic marker), confocal microscopy and Neurolucida 360 software to trace, digitize, and quantitatively map the topographical distribution of the sympathetic postganglionic innervation in whole atria of C57Bl/6 J mice. We found that (1) 4–5 major extrinsic TH-IR nerve bundles entered the atria at the superior vena cava, right atrium (RA), left precaval vein and the root of the pulmonary veins (PVs) in the left atrium (LA). Although these bundles projected to different areas of the atria, their projection fields partially overlapped. (2) TH-IR axon and terminal density varied considerably between different sites of the atria with the greatest density of innervation near the sinoatrial node region (P < 0.05, n = 6). (3) TH-IR axons also innervated blood vessels and adipocytes. (4) Many principal neurons in intrinsic cardiac ganglia and small intensely fluorescent cells were also strongly TH-IR. Our work provides a comprehensive topographical map of the catecholaminergic efferent axon morphology, innervation, and distribution in the whole atria at single cell/axon/varicosity scale that may be used in future studies to create a cardiac sympathetic-brain atlas.
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