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大鼠腹侧苍白球中多巴胺转运体和酪氨酸羟化酶的区域及亚细胞分隔

Regional and subcellular compartmentation of the dopamine transporter and tyrosine hydroxylase in the rat ventral pallidum.

作者信息

Mengual Elisa, Pickel Virginia M

机构信息

Department of Neurology and Neuroscience, Division of Neurobiology, Weill Medical College of Cornell University, New York, New York 10021, USA.

出版信息

J Comp Neurol. 2004 Jan 12;468(3):395-409. doi: 10.1002/cne.10979.

Abstract

The ventral pallidum (VP) is a major intermediary in the prefrontal cortical circuitry regulating sensorimotor gating and locomotor behavior, both of which are potently modulated by catecholamines. The VP catecholaminergic innervation is derived from midbrain dopaminergic neurons that differ in expression levels of the dopamine transporter (DAT) and from brainstem noradrenergic neurons without DAT. The preferentially low level of DAT in dopaminergic terminals in the prefrontal cortex and in striatal regions projecting more extensively to the VP medial (VPm) compared with VP lateral (VPl) compartment suggests possible region-specific differences in VP axonal distribution of DAT. To test this hypothesis, we examined the electron microscopic localization of DAT and the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), in the VPm and VPl of rat brain. In both regions, DAT and TH were localized primarily in small unmyelinated axons and morphologically heterogeneous axon terminals. DAT-immunogold particles were few in number, but mostly located on the plasma membrane. In contrast, TH immunoreactivity was distributed in the cytoplasm of individual profiles, many of which were without detectable DAT. In comparison with TH, the mean area density of DAT-labeled axons was low throughout the VP. The mean area density of DAT-immunogold axon terminals, however, was significantly higher in VPl than in VPm, whereas that of TH-labeled axons was higher in VPm than in VPl. This dissociation suggests that, compared to the VPl, the VPm receives the greatest input from catecholaminergic afferents that are either nondopaminergic or characterized by having low levels or less terminal distributions of DAT.

摘要

腹侧苍白球(VP)是前额叶皮质回路中调节感觉运动门控和运动行为的主要中间环节,这两者均受到儿茶酚胺的强烈调节。VP的儿茶酚胺能神经支配源自中脑多巴胺能神经元,这些神经元在多巴胺转运体(DAT)的表达水平上存在差异,也源自没有DAT的脑干去甲肾上腺素能神经元。与腹侧苍白球外侧(VPl)区相比,前额叶皮质和纹状体区域中向腹侧苍白球内侧(VPm)投射更广泛的多巴胺能终末中DAT水平较低,这表明DAT在VP轴突分布中可能存在区域特异性差异。为了验证这一假设,我们研究了大鼠脑VPm和VPl中DAT以及儿茶酚胺合成酶酪氨酸羟化酶(TH)的电子显微镜定位。在这两个区域中,DAT和TH主要定位于细小的无髓轴突和形态各异的轴突终末。DAT免疫金颗粒数量很少,但大多位于质膜上。相比之下,TH免疫反应性分布在单个细胞的细胞质中,其中许多细胞未检测到DAT。与TH相比,整个VP中DAT标记轴突的平均面积密度较低。然而,DAT免疫金轴突终末的平均面积密度在VPl中显著高于VPm,而TH标记轴突的平均面积密度在VPm中高于VPl。这种分离表明,与VPl相比,VPm从非多巴胺能或具有低水平或较少终末分布DAT的儿茶酚胺能传入纤维接收的输入最多。

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