Robust presynaptic serotonin 5-HT1B receptor inhibition of the striatonigral output and its sensitization by chronic fluoxetine treatment
Robust presynaptic serotonin 5-HT1B receptor inhibition of the striatonigral output and its sensitization by chronic fluoxetine treatment
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DOI：
10.1152/jn.00831.2014
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发表时间：
2015-05-01
影响因子：
2.5
通讯作者：
Zhou, Fu-Ming
中科院分区：
文献类型：
--
作者：
Ding, Shengyuan;Li, Li;Zhou, Fu-Ming
纹状体黑质投射是纹状体输出通路，对运动控制、认知和情绪调节至关重要。黑质网状部（substantia nigra pars reticulata，SNr）的轴突终末表达高水平的5-HT 1B型受体（5-HT 1B Rs），而SNr也接受表达5-HT转运体的强烈5-HT神经支配，这为基于5-HT和选择性5-HT再摄取抑制剂（selective 5-HT reuptake inhibitor，SSRI）的抗抑郁治疗提供了解剖学基础以调节纹状体黑质输出。在这篇文章中，我们表明，5-HT，通过激活突触前5-HT（1B）受体的纹状体黑质轴突终末，有力地抑制纹状体黑质GABA输出，反映在减少纹状体黑质抑制性突触后电流SNr GABA神经元。在功能上，5-HT 1BR激动减少了纹状体黑质GABA输出诱导的SNr GABA神经元自发高频放电暂停。同样重要的是，氟西汀的慢性SSRI治疗增强了SNr GABA神经元突触前5-HT 1BR介导的停顿减少。总之，这些结果表明，激活纹状体黑质轴突终末上的5-HT（1B）Rs可以限制促进运动的GABA输出。此外，与5-HT 1自身受体的脱敏相反，基于SSRI的慢性抗抑郁药治疗使SNr中的这种突触前5-HT 1BR介导的作用变得敏感，这是一种改变纹黑质信息传递的新型细胞机制，可能有助于慢性SSRI治疗的行为效应。
The striatonigral projection is a striatal output pathway critical to motor control, cognition, and emotion regulation. Its axon terminals in the substantia nigra pars reticulata (SNr) express a high level of serotonin (5-HT) type 1B receptors (5-HT1B Rs), whereas the SNr also receives an intense 5-HT innervation that expresses 5-HT transporters, providing an anatomic substrate for 5-HT and selective 5-HT reuptake inhibitor (SSRI)-based antidepressant treatment to regulate the striatonigral output. In this article we show that 5-HT, by activating presynaptic 5-HT(1B)Rs on the striatonigral axon terminals, potently inhibited the striatonigral GABA output, as reflected in the reduction of the striatonigral inhibitory postsynaptic currents in SNr GABA neurons. Functionally, 5-HT1BR agonism reduced the striatonigral GABA output-induced pause of the spontaneous high-frequency firing in SNr GABA neurons. Equally important, chronic SSRI treatment with fluoxetine enhanced this presynaptic 5-HT1BR-mediated pause reduction in SNr GABA neurons. Taken together, these results indicate that activation of the 5-HT(1B)Rs on the striatonigral axon terminals can limit the motor-promoting GABA output. Furthermore, in contrast to the desensitization of 5-HT1 autoreceptors, chronic SSRI-based antidepressant treatment sensitizes this presynaptic 5-HT1BR-mediated effect in the SNr, a novel cellular mechanism that alters the striatonigral information transfer, potentially contributing to the behavioral effects of chronic SSRI treatment.