Presynaptic localization of an AMPA-type glutamate receptor in corticostriatal and thalamostriatal axon terminals

Presynaptic localization of an AMPA-type glutamate receptor in corticostriatal and thalamostriatal axon terminals
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DOI:
10.1111/j.1460-9568.2004.03807.x
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发表时间:
2004-12-01
影响因子:
3.4
通讯作者:
Kaneko, T
Kaneko, T
中科院分区:
医学3区
文献类型:
--
作者:
Fujiyama, F;Kuramoto, E;Kaneko, T

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已知新纹状体接收来自大脑皮层和丘脑核的谷氨酸能投射。囊泡谷氨酸转运蛋白 1 和 2(VGluT1 和 VGluT2)分别位于皮质纹状体和丘脑纹状体传入神经的轴突末端,而 VGluT3 位于新纹状体胆碱能中间神经元的轴突末端。在本研究中,通过双标记 VGluT 和谷氨酸受体的包埋后免疫金方法,检查了大鼠新纹状体中离子型谷氨酸受体的突触后定位。 AMPA 受体亚基 GluR1 和 GluR2/3 的免疫反应性金颗粒不仅经常出现在突触后,而且还出现在新纹状体中 VGluT1 和 VGluT2 免疫阳性的突触前特征上,并且在 VGluT1 阳性的突触后和突触前特征上观察到 GluR4 免疫反应性颗粒。定量分析显示,在新纹状体 VGluT1 或 VGluT2 阳性突触结构中发现的 GluR1-、GluR2-、GluR2/3- 和 GluR4- 免疫阳性颗粒中有 27 - 45% 与 VGluT 阳性轴突的突触前特征相关。相比之下,新纹状体中的 VGluT 阳性突触前特征显示,NMDA 受体亚基 NR1 或 NR2A/B 几乎没有免疫反应性。此外,在新纹状体中形成不对称突触的 VGluT3 阳性(胆碱能)末端的突触前特征中,或者在新皮质中的 VGluT1 或 VGluT2 阳性末端的突触前特征中,几乎没有观察到 GluR2/3 免疫阳性颗粒。目前的结果表明,AMPA 受体亚基而非 NMDA 受体亚基位于皮质纹状体和丘脑纹状体传入神经的轴突末端,并表明从这些轴突末端释放的谷氨酸通过突触前 AMPA 自身受体控制末端的活性。
The neostriatum is known to receive glutamatergic projections from the cerebral cortex and thalamic nuclei. Vesicular glutamate transporters 1 and 2 (VGluT1 and VGluT2) are located on axon terminals of corticostriatal and thalamostriatal afferents, respectively, whereas VGluT3 is found in axon terminals of cholinergic interneurons in the neostriatum. In the present study, the postsynaptic localization of ionotropic glutamate receptors was examined in rat neostriatum by the postembedding immunogold method for double labelling of VGluT and glutamate receptors. Immunoreactive gold particles for AMPA receptor subunits GluR1 and GluR2/3 were frequently found not only on postsynaptic but also on presynaptic profiles immunopositive for VGluT1 and VGluT2 in the neostriatum, and GluR4-immunoreactive particles were observed on postsynaptic and presynaptic profiles positive for VGluT1. Quantitative analysis revealed that 27 - 45% of GluR1-, GluR2-, GluR2/3- and GluR4-immunopositive particles found in VGluT1- or VGluT2-positive synaptic structures in the neostriatum were associated with the presynaptic profiles of VGluT-positive axons. In contrast, VGluT-positive presynaptic profiles in the neostriatum showed almost no immunoreactivity for NMDA receptor subunits NR1 or NR2A/B. Furthermore, almost no GluR2/3- immunopositive particles were observed in presynaptic profiles of VGluT3-positive ( cholinergic) terminals that made asymmetric synapses in the neostriatum, or in those of VGluT1- or VGluT2-positive terminals in the neocortex. The present results indicate that AMPA receptor subunits but not NMDA receptor subunits are located on axon terminals of corticostriatal and thalamostriatal afferents, and suggest that glutamate released from these axon terminals controls the activity of the terminals through the presynaptic AMPA autoreceptors.