5-HT1B receptor-mediated presynaptic inhibition of GABA release in the suprachiasmatic nucleus
5-HT1B receptor-mediated presynaptic inhibition of GABA release in the suprachiasmatic nucleus
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DOI：
10.1152/jn.00770.2004
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发表时间：
2005-06-01
影响因子：
2.5
通讯作者：
Dudek, FE
中科院分区：
文献类型：
--
作者：
Bramley, JR;Sollars, PJ;Dudek, FE
视交叉上核（SCN）接受密集的5-HT能神经支配，通过视网膜视交叉能末梢上的5-HT 1B（5-HT 1B）突触前受体调节到SCN的光输入。然而，SCN中的大多数5-HT 1B结合位点位于非视网膜终末，SCN中的大多数轴突终末是GABA能的。因此，我们通过检测高选择性5-HT 1B受体激动剂CP-93，129对SCN微型抑制性突触后电流（mIPSC）的影响，验证了5-HT 1B受体也可能位于SCN GABA能末梢的假设。从大鼠和小鼠下丘脑切片中的SCN神经元获得mIPSC的全细胞膜片钳记录。使用含有CsCl的微电极与QX 314，我们分离的mPSC是敏感的GABA A受体拮抗剂，荷包牡丹碱。CP-93，129（1 μ M）的浴涂在大鼠SCN神经元中使mIPSC的频率平均降低22%（n = 7），在小鼠SCN神经元中使mIPSC的频率平均降低30%（n = 8），对mIPSC振幅没有明显影响。在缺乏功能性5-HT 1B受体的小鼠中，CP-93，129（1 μ M）对任何测试细胞（n = 4）中记录的mIPSC的频率或振幅没有明显影响。由选择性5-HT 1B受体激动剂CP-93，129产生的SCN神经元mIPSC频率的降低与以下解释一致：5- HT 1B受体位于SCN中的GABA末端上，并且5-HT通过5-HT 1B突触前受体介导的机制抑制GABA释放。
The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that modulates photic input to the SCN via serotonin 1B (5-HT1B) presynaptic receptors on retinal glutamatergic terminals. However, the majority of 5-HT1B binding sites in the SCN are located on nonretinal terminals and most axonal terminals in the SCN are GABAergic. We therefore tested the hypothesis that 5-HT1B receptors might also be located on SCN GABAergic terminals by examining the effects of the highly selective 5-HT1B receptor agonist CP-93,129 on SCN miniature inhibitory postsynaptic currents (mIPSCs). Whole cell patch-clamp recordings of mIPSCs were obtained from rat and mouse SCN neurons in hypothalamic slices. Using CsCl-containing microelectrodes with QX314, we isolated mPSCs that were sensitive to the GABA A receptor antagonist, bicuculline. Bath application of CP-93,129 (1 mu M) decreased the frequency of mIPSCs by an average of 22% (n = 7) in rat SCN neurons and by an average of 30% (n = 8) in mouse SCN neurons with no clear effect on mIPSC amplitude. In mice lacking functional 5-HT1B receptors, CP-93,129 (1 mu M) had no clear effect on the frequency or the amplitude of mIPSCs recorded in any of the cells tested (n = 4). The decrease in the frequency of mIPSCs of SCN neurons produced by the selective 5-HT1B receptor agonist CP-93,129 is consistent with the interpretation that 5- HT 1B receptors are located on GABA terminals in the SCN and that 5-HT inhibits GABA release via a 5-HT1B presynaptic receptor-mediated mechanism.