5-HT2A receptor-mediated excitation on cerebellar fastigial nucleus neurons and promotion of motor behaviors in rats
5-HT2A receptor-mediated excitation on cerebellar fastigial nucleus neurons and promotion of motor behaviors in rats
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5-HT2A受体介导的小脑顶核神经元兴奋及促进大鼠运动行为
DOI：
10.1007/s00424-013-1378-x
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发表时间：
2014
影响因子：
4.5
通讯作者：
Jian-Jun Wang
中科院分区：
文献类型：
--
作者：
Chang-Zheng Zhang;Qian-Xing Zhuang;Ye-Cheng He;Guang-Ying Li;Jing-Ning Zhu;Jian-Jun Wang
人们早就知道，5-羟色胺能传入是小脑中仅次于苔藓纤维和攀缘纤维的第三大传入群体。然而，5-羟色胺能输入在小脑介导的运动行为中的作用仍然很大程度上是未知的。在这里，我们发现在5-HT2受体亚家族中只有5-HT2A受体在大鼠小脑顶核(FN)表达和定位，FN是脊髓小脑精确调节躯干和肢体运动的最终产物之一。值得注意的是，选择性激活5-HT2A受体在体外以浓度依赖的方式对FN神经元产生突触后兴奋效应，这与5-HT对同一受试神经元的兴奋作用是一致的。选择性5-HT2A受体拮抗剂M100907可浓度依赖性地阻断5-羟色胺和5-HT2A受体激动剂TCB-2对FN神经元的兴奋作用。因此，双侧丘脑束核内微量注射5-羟色胺可显著提高大鼠在加速转杆和平衡木上的运动成绩，并缩小运动步态的步幅而不是步长。所有这些运动行为效应与FN选择性激活5-HT2A受体的结果高度一致，阻断FN内5-HT2A受体介导的内源性5-羟色胺能传入成分可显著削弱这些运动行为。以上结果表明，突触后5-HT2A受体在5-羟色胺对小脑FN神经元的兴奋作用和对FN相关运动行为的促进中起重要作用，提示5-羟色胺能传入物质可能通过直接调节脊髓小脑的最终输出而参与小脑运动控制。
It has long been known that serotonergic afferent inputs are the third largest afferent population in the cerebellum after mossy fibers and climbing fibers. However, the role of serotonergic inputs in cerebellar-mediated motor behaviors is still largely unknown. Here, we show that only 5-HT2A receptors among the 5-HT2 receptor subfamily are expressed and localized in the rat cerebellar fastigial nucleus (FN), one of the ultimate outputs of the spinocerebellum precisely regulating trunk and limb movements. Remarkably, selective activation of 5-HT2A receptors evokes a postsynaptic excitatory effect on FN neurons in a concentration-dependent manner in vitro, which is in accord with the 5-HT-elicited excitation on the same tested neurons. Furthermore, selective 5-HT2A receptor antagonist M100907 concentration-dependently blocks the excitatory effects of 5-HT and TCB-2, a 5-HT2A receptor agonist, on FN neurons. Consequently, microinjection of 5-HT into bilateral FNs significantly promotes rat motor performances on accelerating rota-rod and balance beam and narrows stride width rather than stride length in locomotion gait. All these motor behavioral effects are highly consistent with those of selective activation of 5-HT2A receptors in FNs, and blockage of the component of 5-HT2A receptor-mediated endogenous serotonergic inputs in FNs markedly attenuates these motor performances. All these results demonstrate that postsynaptic 5-HT2A receptors greatly contribute to the 5-HT-mediated excitatory effect on cerebellar FN neurons and promotion of the FN-related motor behaviors, suggesting that serotonergic afferent inputs may actively participate in cerebellar motor control through their direct modulation on the final output of the spinocerebellum.