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小脑深部核团中GABA能细胞和非GABA能细胞之间的GABA能突触通讯。

GABAergic synaptic communication in the GABAergic and non-GABAergic cells in the deep cerebellar nuclei.

作者信息

Uusisaari M, Knöpfel T

机构信息

Laboratory for Neuronal Circuit Dynamics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.

出版信息

Neuroscience. 2008 Oct 15;156(3):537-49. doi: 10.1016/j.neuroscience.2008.07.060. Epub 2008 Aug 6.

Abstract

The deep cerebellar nuclei (DCN) are the final integrative units of the cerebellar network. The strongest single afferent to the DCN is formed by GABAergic Purkinje neuron axons whose synapses constitute the majority of all synapses in the DCN, with their action strongly regulating the intrinsic activity of their target neurons. Although this is well established, it remains unclear whether all DCN cell groups receive a functionally similar inhibitory input. We previously characterized three types of mouse DCN neurons based on the expression of glutamic acid decarboxylase isoform 67 (GAD67), their active membrane properties and morphological features. Here we describe the GABAergic synapses in these cell groups and show that spontaneous GABAergic synaptic activity can be seen in all three cell types. Since the majority of DCN neurons fire action potentials spontaneously at high frequencies both in vivo and in vitro, we expected that spontaneous GABAergic synaptic activities mediated by intra-DCN synaptic connections could be uncovered by their sensitivity to TTX. However, TTX had little effect on spontaneous synaptic activity. It seems, therefore that functional GABAergic connectivity within the DCN is sparse and/or weak at least under our experimental conditions. Even though present in all cell types, the spontaneous GABAergic events showed significant differences between the cell types. The synaptic currents in GABAergic cells had lower amplitude, lower frequency and slower kinetics than those of non-GABAergic cells. These differences could not be sufficiently explained by considering only cell size differences or a differential GABA(A)-receptor alpha-subunit composition. Rather, the main differentiating factor appears to be the dendritic localization of GABAergic synapses in the GABAergic cells.

摘要

小脑深部核团(DCN)是小脑网络的最终整合单元。对DCN最强的单一传入神经是由γ-氨基丁酸(GABA)能浦肯野神经元轴突形成的,其突触构成了DCN中所有突触的大部分,它们的作用强烈调节其靶神经元的内在活动。尽管这一点已得到充分证实,但尚不清楚所有DCN细胞群是否都接受功能相似的抑制性输入。我们之前根据谷氨酸脱羧酶同工型67(GAD67)的表达、它们的活跃膜特性和形态特征对三种类型的小鼠DCN神经元进行了表征。在这里,我们描述了这些细胞群中的GABA能突触,并表明在所有三种细胞类型中都可以看到自发的GABA能突触活动。由于大多数DCN神经元在体内和体外都以高频自发发放动作电位,我们预计由DCN内突触连接介导的自发GABA能突触活动可以通过它们对河豚毒素(TTX)的敏感性来揭示。然而,TTX对自发突触活动几乎没有影响。因此,至少在我们的实验条件下,DCN内功能性GABA能连接似乎是稀疏的和/或微弱的。尽管在所有细胞类型中都存在,但自发的GABA能事件在细胞类型之间表现出显著差异。GABA能细胞中的突触电流比非GABA能细胞的突触电流幅度更低、频率更低且动力学更慢。仅考虑细胞大小差异或GABA(A)受体α亚基组成的差异无法充分解释这些差异。相反,主要的区分因素似乎是GABA能突触在GABA能细胞中的树突定位。

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