Modulatory effects of serotonin on glutamatergic synaptic transmission and long-term depression in the deep cerebellar nuclei

Modulatory effects of serotonin on glutamatergic synaptic transmission and long-term depression in the deep cerebellar nuclei
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DOI:
10.1016/j.neuroscience.2010.10.037
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发表时间:
2011-01
期刊:
影响因子:
3.3
通讯作者:
M. Murano;F. Saitow;H. Suzuki
M. Murano;F. Saitow;H. Suzuki
中科院分区:
医学3区
文献类型:
--
作者:
M. Murano;F. Saitow;H. Suzuki

文献摘要

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小脑深核(DCN)是小脑回路的终末成分,构成小脑回路的主要输出结构。它们的活动对于某些形式的运动学习以及运动的产生和控制很重要。DCN神经元通过苔藓纤维(MF)接受来自脑桥核的多巴胺能兴奋性输入,并同时接受来自中缝核含5-HT神经元的输入。本研究采用11 ~ 15日龄大鼠小脑脑片,探讨5-HT在MF-DCN突触中的作用。浴用5-HT可通过激活MFs突触前末梢的5-HT 1B受体可逆地降低刺激诱发的兴奋性突触后电流(eEPSC)的幅度。突发刺激的MF引起的长期抑郁症(LTD)的MF-DCN突触,需要激活组I代谢型谷氨酸受体(mGluR)。在5-HT的存在下,MF EPSCs的爆发诱导LTD的程度显着降低。应用5-HT也降低了由类似爆发刺激诱发的mGluR依赖性慢EPSC的幅度。此外,Ⅰ组mGluR激动剂(S)-3,5-二羟基苯甘氨酸(DHPG)可诱导MF EPSC的化学LTD,而5-HT对此LTD无明显影响。结果表明,5-HT不仅对MF EPSC有短暂的抑制作用,而且在调节长时程突触效能中起作用。
The deep cerebellar nuclei (DCN) are the terminal components of the cerebellar circuitry and constitute its primary output structure. Their activity is important for certain forms of motor learning as well as generation and control of movement. DCN neurons receive glutamatergic excitatory inputs from the pontine nuclei via mossy fibres (MFs) and concomitantly receive inputs from 5-HT-containing neurons of the raphe nuclei. We aimed to explore the roles of 5-HT at MF–DCN synapses by using cerebellar slices from 11 to 15-day-old rats. Bath application of 5-HT reversibly decreased the amplitude of stimulation-evoked excitatory postsynaptic currents (eEPSCs) via the activation of 5-HT1Breceptors at the presynaptic terminals of the MFs. Burst stimulation of the MFs elicited long-term depression (LTD) at the MF–DCN synapses that require activation of the group I metabotropic glutamate receptor (mGluR). In the presence of 5-HT, the extent of burst-induced LTD of MF EPSCs was significantly reduced. Application of 5-HT also decreased the amplitude of mGluR-dependent slow EPSCs evoked by similar burst stimulation. Furthermore, (S)-3,5-dihydroxyphenylglycine (DHPG), a group I mGluR agonist, induced chemical LTD of MF EPSCs, and 5-HT had no significant effect on this LTD. Taken together, the results suggest that 5-HT not only has transitory inhibitory effects on MF EPSCs but also plays a role in regulating the long-term synaptic efficacy.