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5-HT2A receptor-mediated excitation on cerebellar fastigial nucleus neurons and promotion of motor behaviors in rats

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Abstract

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.

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Acknowledgments

The work was supported by grants 31070959, 31071021, 31171050, 31330033, and 91332124 from the National Natural Science Foundation of China; RFDP grant 20100091110016 and NCET Program from the State Educational Ministry of China; grant BK2011014 from the Natural Science Foundation of Jiangsu Province, China; and grant 2013T60520 from China Postdoctoral Science Foundation.

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  1. Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Mailbox 426, 22 Hankou Road, Nanjing, 210093, China

    Chang-Zheng Zhang, Qian-Xing Zhuang, Ye-Cheng He, Guang-Ying Li, Jing-Ning Zhu & Jian-Jun Wang

  2. School of Life Sciences, Anqing Normal University, 128 South Linghu Road, Anqing, 246011, China

    Chang-Zheng Zhang

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  1. Chang-Zheng Zhang
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Correspondence to Jing-Ning Zhu or Jian-Jun Wang.

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Chang-Zheng Zhang and Qian-Xing Zhuang contributed equally to this work.

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Zhang, CZ., Zhuang, QX., He, YC. et al. 5-HT2A receptor-mediated excitation on cerebellar fastigial nucleus neurons and promotion of motor behaviors in rats. Pflugers Arch - Eur J Physiol 466, 1259–1271 (2014). https://doi.org/10.1007/s00424-013-1378-x

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