Prolonged postinhibitory rebound firing in the cerebellar nuclei mediated by group I metabotropic glutamate receptor potentiation of L-type calcium currents.
Prolonged postinhibitory rebound firing in the cerebellar nuclei mediated by group I metabotropic glutamate receptor potentiation of L-type calcium currents.
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DOI：
10.1523/jneurosci.1834-11.2011
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发表时间：
2011-07-13
期刊：
影响因子：
--
通讯作者：
Raman IM
中科院分区：
文献类型：
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作者：
Zheng N;Raman IM
小脑核中的神经元在突触抑制序列中断自发放电后，以加速的速率长时间放电。然而，无论是在体外还是在体内，这种长时间的反弹放电都受到传入神经的强烈刺激的青睐，这表明GABA以外的神经递质可能有助于提高放电率。在这里，我们测试是否代谢型谷氨酸受体调节小鼠小脑切片核细胞的兴奋性。在电流钳中，高频突触刺激后延长的反弹放电率被各种I组mGluR拮抗剂，包括CPCCOEt，（7-（羟基亚氨基）环丙烯并[B]色烯-1a-羧酸乙酯），JNJ 16259685（（3，4-二氢-2H-吡喃并[2，3-B]喹啉-7-基）-（顺式-4-甲氧基环己基）-甲酮）+MPEP，或3-MATIDA（α-氨基-5-羧基-3-甲基-2-噻吩乙酸）+MPEP，只要mGluR 1和mGluR 5都被阻断。这种mGluR依赖性的放电加速减少，但当IPSP被GABAA受体拮抗剂阻止时仍然明显。在电压钳中，电压斜坡揭示了非失活的、低电压激活的尼莫地平敏感电流，该电流被选择性I组mGluR激动剂s-DHPG（（S）-3，5-二羟基苯甘氨酸）增强。这种假定的L型电流也增加时，mGluRs被激活的列车诱发的突触电流，而不是直接应用激动剂。在电流钳，阻断L-型钙通道与特定的阻断剂硝苯地平大大减少了长期的刺激后放电和闭塞的影响，添加组I mGluR拮抗剂。因此，突触释放的谷氨酸盐对低电压激活的L型电流的增强作用几乎完全解释了mGluR依赖性的放电加速。总之，这些数据表明，在体内的小脑核中的长期反弹发射是最有可能发生时，GABAA和mGluRs同时激活并发的兴奋和抑制。
Neurons in the cerebellar nuclei fire at accelerated rates for prolonged periods after trains of synaptic inhibition that interrupt spontaneous firing. Both in vitro and in vivo, however, this prolonged rebound firing is favored by strong stimulation of afferents, suggesting that neurotransmitters other than GABA may contribute to the increased firing rates. Here, we tested whether metabotropic glutamate receptors modulate excitability of nuclear cells in cerebellar slices from mouse. In current clamp, the prolonged rebound firing rate after high-frequency synaptic stimulation was reduced by a variety of group I mGluR antagonists, including CPCCOEt (7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester), JNJ16259685 ((3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone)+MPEP, or 3-MATIDA (α-amino-5-carboxy-3-methyl-2-thiopheneacetic acid) +MPEP, as long as both mGluR1 and mGluR5 were blocked. This mGluR-dependent acceleration of firing was reduced but still evident when IPSPs were prevented by GABAA receptor antagonists. In voltage clamp, voltage ramps revealed a non-inactivating, low-voltage-activated, nimodipine-sensitive current that was enhanced by the selective group I mGluR agonist s-DHPG ((S)-3,5-dihydroxyphenylglycine). This putative L-type current also increased when mGluRs were activated by trains of evoked synaptic currents instead of direct application of agonist. In current clamp, blocking L-type Ca channels with the specific blocker nifedipine greatly reduced prolonged post-stimulus firing and occluded the effect of adding group I mGluR antagonists. Thus, potentiation of a low-voltage-activated L-type current by synaptically released glutamate accounted nearly fully for the mGluR-dependent acceleration of firing. Together, these data suggest that prolonged rebound firing in the cerebellar nuclei in vivo is most likely to occur when GABAA and mGluRs are simultaneously activated by concurrent excitation and inhibition.