Waldvogel Henry J, Billinton Andy, White Julia H, Emson Piers C, Faull Richard L M
Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
J Comp Neurol. 2004 Mar 15;470(4):339-56. doi: 10.1002/cne.20005.
The GABA(B) receptor is a G-protein linked metabotropic receptor that is comprised of two major subunits, GABA(B)R1 and GABA(B)R2. In this study, the cellular distribution of the GABA(B)R1 and GABA(B)R2 subunits was investigated in the normal human basal ganglia using single and double immunohistochemical labeling techniques on fixed human brain tissue. The results showed that the GABA(B) receptor subunits GABA(B)R1 and GABA(B)R2 were both found on the same neurons and followed the same distribution patterns. In the striatum, these subunits were found on the five major types of interneurons based on morphology and neurochemical labeling (types 1, 2, 3, 5, 6) and showed weak labeling on the projection neurons (type 4). In the globus pallidus, intense GABA(B)R1 and GABA(B)R2 subunit labeling was found in large pallidal neurons, and in the substantia nigra, both pars compacta and pars reticulata neurons were labeled for both receptor subunits. Studies investigating the colocalization of the GABA(A) alpha(1) subunit and GABA(B) receptor subunits showed that the GABA(A) receptor alpha(1) subunit and the GABA(B)R1 subunit were found together on GABAergic striatal interneurons (type 1 parvalbumin, type 2 calretinin, and type 3 GAD neurons) and on neurons in the globus pallidus and substantia nigra pars reticulata. GABA(B)R1 and GABA(B)R2 were found on substantia nigra pars compacta neurons but the GABA(A) receptor alpha(1) subunit was absent from these neurons. The results of this study provide the morphological basis for GABAergic transmission within the human basal ganglia and provides evidence that GABA acts through both GABA(A) and GABA(B) receptors. That is, GABA acts through GABA(B) receptors, which are located on most of the cell types of the striatum, globus pallidus, and substantia nigra. GABA also acts through GABA(A) receptors containing the alpha(1) subunit on specific striatal GABAergic interneurons and on output neurons of the globus pallidus and substantia nigra pars reticulata.
γ-氨基丁酸B（GABA(B)）受体是一种与G蛋白偶联的代谢型受体，由两个主要亚基GABA(B)R1和GABA(B)R2组成。在本研究中，使用固定人脑组织的单免疫组化和双免疫组化标记技术，对正常人类基底神经节中GABA(B)R1和GABA(B)R2亚基的细胞分布进行了研究。结果显示，GABA(B)受体亚基GABA(B)R1和GABA(B)R2均存在于同一神经元上，并遵循相同的分布模式。在纹状体中，基于形态学和神经化学标记，这些亚基存在于五种主要类型的中间神经元（1型、2型、3型、5型、6型）上，而在投射神经元（4型）上显示出较弱的标记。在苍白球中，在大型苍白球神经元中发现了强烈的GABA(B)R1和GABA(B)R2亚基标记，在黑质中，致密部和网状部的神经元均被这两种受体亚基标记。研究GABA(A)α(1)亚基与GABA(B)受体亚基共定位的结果表明，GABA(A)受体α(1)亚基和GABA(B)R1亚基共同存在于GABA能纹状体中间神经元（1型小白蛋白、2型钙视网膜蛋白和3型谷氨酸脱羧酶神经元）以及苍白球和黑质网状部的神经元上。在黑质致密部神经元上发现了GABA(B)R1和GABA(B)R2，但这些神经元中不存在GABA(A)受体α(1)亚基。本研究结果为人类基底神经节内的GABA能传递提供了形态学基础，并证明GABA通过GABA(A)和GABA(B)受体发挥作用。也就是说，GABA通过位于纹状体、苍白球和黑质的大多数细胞类型上的GABA(B)受体发挥作用。GABA还通过特定纹状体GABA能中间神经元以及苍白球和黑质网状部的输出神经元上含有α(1)亚基的GABA(A)受体发挥作用。
