Dept of Hearing and Speech Sciences, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Hear Res. 2011 Apr;274(1-2):129-41. doi: 10.1016/j.heares.2010.11.001. Epub 2010 Nov 24.
The vesicular glutamate transporters (VGLUTs) regulate the storage and release of glutamate in the brain. In adult animals, the VGLUT1 and VGLUT2 isoforms are widely expressed and differentially distributed, suggesting that neural circuits exhibit distinct modes of glutamate regulation. Studies in rodents suggest that VGLUT1 and VGLUT2 mRNA expression patterns are partly complementary, with VGLUT1 expressed at higher levels in the cortex and VGLUT2 prominent subcortically, but with overlapping distributions in some nuclei. In primates, VGLUT gene expression has not been previously studied in any part of the brain. The purposes of the present study were to document the regional expression of VGLUT1 and VGLUT2 mRNA in the auditory pathway through A1 in the cortex, and to determine whether their distributions are comparable to rodents. In situ hybridization with antisense riboprobes revealed that VGLUT2 was strongly expressed by neurons in the cerebellum and most major auditory nuclei, including the dorsal and ventral cochlear nuclei, medial and lateral superior olivary nuclei, central nucleus of the inferior colliculus, sagulum, and all divisions of the medial geniculate. VGLUT1 was densely expressed in the hippocampus and ventral cochlear nuclei, and at reduced levels in other auditory nuclei. In the auditory cortex, neurons expressing VGLUT1 were widely distributed in layers II-VI of the core, belt and parabelt regions. VGLUT2 was expressed most strongly by neurons in layers IIIb and IV, weakly by neurons in layers II-IIIa, and at very low levels in layers V-VI. The findings indicate that VGLUT2 is strongly expressed by neurons at all levels of the subcortical auditory pathway, and by neurons in the middle layers of the cortex, whereas VGLUT1 is strongly expressed by most if not all glutamatergic neurons in the auditory cortex and at variable levels among auditory subcortical nuclei. These patterns imply that VGLUT2 is the main vesicular glutamate transporter in subcortical and thalamocortical (TC) circuits, whereas VGLUT1 is dominant in corticocortical (CC) and corticothalamic (CT) systems of projections. The results also suggest that VGLUT mRNA expression patterns in primates are similar to rodents, and establish a baseline for detailed studies of these transporters in selected circuits of the auditory system.
囊泡谷氨酸转运体（VGLUTs）调节大脑中谷氨酸的储存和释放。在成年动物中，VGLUT1 和 VGLUT2 同工型广泛表达且分布不同，表明神经回路表现出不同的谷氨酸调节模式。在啮齿动物中的研究表明，VGLUT1 和 VGLUT2 mRNA 表达模式部分互补，VGLUT1 在皮层中表达水平较高，而 VGLUT2 在皮层下突出，但在一些核中存在重叠分布。在灵长类动物中，以前尚未在大脑的任何部位研究过 VGLUT 基因表达。本研究的目的是记录 VGLUT1 和 VGLUT2 mRNA 在听觉通路上的表达，从皮层的 A1 到听觉中枢核团，并确定其分布是否与啮齿动物相似。用反义核糖探针进行原位杂交显示，VGLUT2 在小脑和大多数主要听觉核团（包括背侧和腹侧耳蜗核、内侧和外侧上橄榄核、下丘中央核、 sagulum 和内侧膝状体的所有核团）的神经元中强烈表达。VGLUT1 在海马体和腹侧耳蜗核中高度表达，而在其他听觉核团中的表达水平降低。在听觉皮层中，表达 VGLUT1 的神经元广泛分布于核心、带和副带区的 II-VI 层。VGLUT2 在 IIIb 和 IV 层的神经元中表达最强，在 II-IIIa 层的神经元中表达较弱，在 V-VI 层的神经元中表达非常低。这些发现表明，VGLUT2 在皮质下听觉通路的各级神经元以及皮层中间层的神经元中强烈表达，而 VGLUT1 在听觉皮层中的大多数（如果不是全部）谷氨酸能神经元以及在听觉皮质下核团中的不同水平中强烈表达。这些模式表明，VGLUT2 是皮质下和丘脑皮质（TC）回路中的主要囊泡谷氨酸转运体，而 VGLUT1 在皮质皮质（CC）和皮质丘脑（CT）投射系统中占主导地位。研究结果还表明，灵长类动物的 VGLUT mRNA 表达模式与啮齿动物相似，为在听觉系统的选定回路中对这些转运体进行详细研究奠定了基础。
