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小脑深部核团中的甘氨酸能突触电流。

Glycinergic synaptic currents in the deep cerebellar nuclei.

作者信息

Pedroarena Christine M, Kamphausen Susanne

机构信息

Department of Cognitive Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Otfried Müller Strasse 27, 72076 Tübingen, Germany.

出版信息

Neuropharmacology. 2008 Apr;54(5):784-95. doi: 10.1016/j.neuropharm.2007.12.005. Epub 2007 Dec 23.

Abstract

Despite evidence of local glycinergic circuits in the mature cerebellar nuclei the result of their activation remains unknown. Here, using whole cell recordings in rat cerebellar slices we demonstrated that after postnatal day 17 (>P17) glycinergic IPSCs can be readily evoked in large deep cerebellar nuclear neurons (DCNs), in the same way as in neonatal DCNs (P7-P10). Spontaneous glycinergic IPSCs were very rare but direct presynaptic depolarization by superfusion with elevated potassium concentration or application of 4-aminopyridine consistently evoked strychnine sensitive IPSCs. Glycinergic IPSCs showed fast kinetics in >P17 DCNs while were significantly slower in neonatal DCNs. Immuno-histochemical investigations using a specific marker for glycinergic fibers and terminals showed low density of immuno-fluorescent puncta, putative glycinergic boutons surrounding P18-P23 DCNs, in agreement with the rare spontaneous synaptic activity. But putative glycinergic boutons were present in critical areas for the control of spike generation. In contrast to adult and neonatal DCNs, glycinergic IPSCs could not be induced in juvenile DCNs (P13-P17) despite similar perisomatic immuno-staining pattern and expression of glycinergic receptors to >P17 DCNs. The latter results demonstrate substantial postnatal development of glycinergic cerebellar nuclei circuits. The cerebellum is involved in rapidly controlling ongoing movements. For that function, it is thought important the temporal and spatial precision of its output, which is carried to target structures by DCNs. The present study, by demonstrating fast glycinergic IPSCs in mature DCNs, points to the activation of glycinergic microcircuits as one of the possible mechanism involved in the spatio-temporal control of cerebellar output.

摘要

尽管在成熟的小脑核中有局部甘氨酸能回路的证据,但其激活的结果仍不清楚。在这里,我们使用大鼠小脑切片的全细胞记录表明,在出生后第17天(>P17)之后,甘氨酸能抑制性突触后电流(IPSCs)能够很容易地在大型小脑深部核神经元(DCNs)中诱发,方式与新生DCNs(P7 - P10)相同。自发性甘氨酸能IPSCs非常罕见,但通过用升高的钾浓度进行灌流或应用4 - 氨基吡啶进行直接突触前去极化,始终能诱发士的宁敏感的IPSCs。甘氨酸能IPSCs在>P17的DCNs中表现出快速动力学,而在新生DCNs中则明显较慢。使用甘氨酸能纤维和终末的特异性标记物进行的免疫组织化学研究表明,围绕P18 - P23 DCNs的免疫荧光斑点(推测为甘氨酸能终扣)密度较低,这与罕见的自发性突触活动一致。但推测的甘氨酸能终扣存在于控制动作电位产生的关键区域。与成年和新生DCNs不同,尽管幼年DCNs(P13 - P17)的胞体周围免疫染色模式和甘氨酸能受体表达与>P17的DCNs相似,但仍无法诱导出甘氨酸能IPSCs。后一结果表明甘氨酸能小脑核回路在出生后有显著发育。小脑参与快速控制正在进行的运动。对于该功能,人们认为其输出的时间和空间精度很重要,而输出是由DCNs传递到目标结构的。本研究通过在成熟DCNs中证明快速的甘氨酸能IPSCs,指出甘氨酸能微回路的激活是参与小脑输出时空控制的可能机制之一。

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