Presynaptic and postsynaptic GABAA receptors in rat suprachiasmatic nucleus
Presynaptic and postsynaptic GABAA receptors in rat suprachiasmatic nucleus
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DOI：
10.1016/s0306-4522(03)00062-9
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Yarom, Y
中科院分区：
文献类型：
--
作者：
Belenky, MA;Sagiv, N;Yarom, Y
哺乳动物视交叉上核（SCN）是大脑的昼夜节律钟，主要由GABA能神经元组成，这些神经元通过突触与GABA（A）受体相互连接。在这里，我们报告这些受体在SCN的亚细胞定位，揭示了一个广泛的特点抗体的α 3亚基的GABA（A）受体结合植入前和植入后的电子显微镜免疫细胞化学。GABA（A）受体免疫反应阳性细胞分布于神经元胞体、树突和轴突终末。在胞体和近端树突中，GABA（A）受体主要表达于内质网和高尔基复合体，而在树突远端，免疫反应产物与突触后质膜相连。植入后免疫金标记显示，许多GABA能轴突终末显示GABA（A）受体免疫反应性，主要与其质膜的突触外部分有关。这些受体的功能进行了研究，在下丘脑切片使用全细胞膜片钳记录的反应，以最小的刺激区域背侧的SCN。诱发的抑制性突触后电流的分析表明，无论是浴或局部应用100 μ M的GABA减少GABA能传递，表现为失败率的两倍增加。在谷氨酸受体阻断剂6-氰基-7-硝基喹喔啉-2，3-二酮和选择性GABA（B）受体阻断剂CGP 55845 A的存在下，这种突触前效应似乎是通过激活GABA（A）受体介导的，因此，我们的结果表明，GABA（A）受体广泛分布于SCN中，并可能在控制哺乳动物的生物钟中起突触前和突触后作用。(C)2003年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
The mammalian suprachiasmatic nucleus (SCN), the brain's circadian clock, is composed mainly of GABAergic neurons, that are interconnected via synapses with GABA(A) receptors. Here we report on the subcellular localization of these receptors in the SCN, as revealed by an extensively characterized antibody to the alpha3 subunit of GABA(A) receptors in conjunction with pre- and postembedding electron microscopic immunocytochemistry. GABA(A) receptor immunoreactivity was observed in neuronal perikarya, dendritic processes and axonal terminals. In perikarya and proximal dendrites, GABA(A) receptor immunoreactivity was expressed mainly in endoplasmic reticulum and Golgi complexes, while in the distal part of dendrites, immunoreaction product was associated with postsynaptic plasma membrane. Many GABAergic axonal terminals, as revealed by postembedding immunogold labeling, displayed GABA(A) receptor immunoreactivity, associated mainly with the extrasynaptic portion of their plasma membrane. The function of these receptors was studied in hypothalamic slices using whole-cell patch-clamp recording of the responses to minimal stimulation of an area dorsal to the SCN. Analysis of the evoked inhibitory postsynaptic currents showed that either bath or local application of 100 muM of GABA decreased GABAergic transmission, manifested as a two-fold increase in failure rate. This presynaptic effect, which was detected in the presence of the glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione and the selective GABA(B) receptor blocker CGP55845A, appears to be mediated via activation of GABA(A) receptors.Our results thus show that GABA(A) receptors are widely distributed in the SCN and may subserve both pre- and postsynaptic roles in controlling the mammalian circadian clock. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.