Presynaptic serotonergic gating of the subthalamonigral glutamatergic projection.
Presynaptic serotonergic gating of the subthalamonigral glutamatergic projection.
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亚腹腔谷氨酸能射击的突触前血清素能门控。
DOI：
10.1523/jneurosci.4111-12.2013
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发表时间：
2013-03-13
期刊：
影响因子：
--
通讯作者：
Zhou FM
中科院分区：
文献类型：
--
作者：
Ding S;Li L;Zhou FM
黑质网状部(SNR)内的GABA能投射神经元是基底节的关键输出神经元。这些神经元的活动受到丘脑底核(STN)谷氨酸能投射的严重影响。SNR还接受强烈的5-羟色胺(5-HT)神经支配，这增加了5-HT可能调节STN→SNR谷氨酸能传递以及随后STN触发SNR神经元放电的可能性。在此，我们发现5-羟色胺减少了刺激STN引起的SNR-GABA神经元的长时程多突触复合体兴奋性突触后电流(EPSCs)。这种抑制5-羟色胺的作用被5-HT1B受体激动剂CP93129模拟，并被5-HT1B拮抗剂NAS-181阻断。5-HT1a受体配基无效。此外，5-羟色胺和CP93129降低了微型EPSCs的频率，但不降低幅度，这表明囊泡释放减少。5-羟色胺和CP93129也降低了SNR-GABA神经元单突触EPSCs的幅度，但增加了成对脉冲比，提示突触前5-HT1B受体对谷氨酸释放有抑制作用。此外，5-羟色胺和CP93129可抑制STN诱发的SNR-→神经元的猝发放电，其中CP93129‘CP93129’对SNR内STN-GABA-SNR轴突终末的抑制作用最强，提示5-HT1B受体在这些轴突终末中起主要作用。最后，5-HT1B受体拮抗剂NAS-181增加了STN触发的复合体EPSCs和SNR GABA神经元的爆发放电，证实了内源性5-HT的作用。这些结果表明，黑质5-羟色胺通过激活突触前5-HT1B受体，阻断兴奋性STN-→-SNR投射，减少SNR-GABA神经元的爆发式放电，从而在运动控制中发挥重要作用。
The GABAergic projection neurons in the substantia nigra pars reticulata (SNr) are key basal ganglia output neurons. The activity of these neurons is critically influenced by the glutamatergic projection from the subthalamic nucleus (STN). The SNr also receives an intense serotonin (5-HT) innervation, raising the possibility that 5-HT may regulate the STN→SNr glutamatergic transmission and the consequent STN-triggered spike firing in SNr neurons. Here we show that 5-HT reduced STN stimulation-evoked long-lasting polysynaptic complex excitatory postsynaptic currents (EPSCs) in SNr GABA neurons. This inhibitory 5-HT effect was mimicked by the 5-HT1B receptor agonist CP93129 and blocked by the 5-HT1B antagonist NAS-181. 5-HT1A receptor ligands were ineffective. Additionally, 5-HT and CP93129 reduced the frequency but not the amplitude of miniature EPSCs, suggesting a reduced vesicular release. 5-HT and CP93129 also decreased the amplitude but increased the paired pulse ratio of the monosynaptic EPSCs in SNr GABA neurons, indicating a presynaptic 5-HT1B receptor-mediated inhibition of glutamate release. Furthermore, 5-HT and CP93129 inhibited STN-triggered burst firing in SNr GABA neurons, and CP93129’s inhibitory effect was strongest when puffed to STN→SNr axon terminals in SNr, indicating a primary role of the 5-HT1B receptors in these axon terminals. Finally, the 5-HT1B receptor antagonist NAS-181 increased the STN-triggered complex EPSCs and burst firing in SNr GABA neurons, demonstrating the effects of endogenous 5-HT. These results suggest that nigral 5-HT, via presynaptic 5-HT1B receptor activation, gates the excitatory STN→SNr projection, reduces burst firing in SNr GABA neurons and thus may play a critical role in movement control.