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小鼠新皮质中细胞类型特异性GABA A受体介导的紧张性抑制

Cell type-specific GABA A receptor-mediated tonic inhibition in mouse neocortex.

作者信息

Vardya Irina, Drasbek Kim R, Dósa Zita, Jensen Kimmo

机构信息

Synaptic Physiology Laboratory, Institute of Physiology and Biophysics, University of Aarhus, Aarhus, Denmark.

出版信息

J Neurophysiol. 2008 Jul;100(1):526-32. doi: 10.1152/jn.01224.2007. Epub 2008 May 7.

Abstract

Activity of extrasynaptic GABA A receptors mediating tonic inhibition is thought to play an important role for the excitability of the mammalian cerebral cortex. However, little is known about the cell type-specific expression of tonic inhibition in particular types of cortical interneurons. Here, we used transgenic mice expressing green fluorescent protein (GFP) in somatostatin-positive (SOM) interneurons and investigated tonic inhibition in SOM interneurons versus pyramidal cells in neocortical layers 2/3. In brain slices, pyramidal cells showed a tonic current of 66 +/- 19 pA in response to the delta-subunit selective GABA A agonist THIP (1 microM). On the other hand, tonic inhibition was absent in SOM interneurons (8 +/- 1 pA) in response to THIP. As opposed to pyramidal cells, SOM interneurons were also insensitive to the delta-subunit preferring neurosteroid allotetrahydrodeoxycorticosterone (THDOC) (100 nM) and to elevated endogenous GABA levels in the slice. Finally, SOM interneurons received only 45% of the phasic charge transfer during GABA A receptor-mediated synaptic activity compared with pyramidal cells. Altogether, our study indicates that SOM interneurons receive relatively weak inhibitory input and cannot be brought under the influence of tonic inhibition.

摘要

介导紧张性抑制的突触外GABA A受体的活性被认为对哺乳动物大脑皮层的兴奋性起着重要作用。然而,对于特定类型的皮层中间神经元中紧张性抑制的细胞类型特异性表达知之甚少。在这里,我们使用在生长抑素阳性(SOM)中间神经元中表达绿色荧光蛋白(GFP)的转基因小鼠,研究了新皮层2/3层中SOM中间神经元与锥体细胞的紧张性抑制。在脑片中,锥体细胞对δ亚基选择性GABA A激动剂THIP(1μM)有66±19 pA的紧张性电流反应。另一方面,SOM中间神经元对THIP无紧张性抑制(8±1 pA)。与锥体细胞不同,SOM中间神经元对偏好δ亚基的神经甾体别四氢脱氧皮质酮(THDOC)(100 nM)和切片中内源性GABA水平升高也不敏感。最后,与锥体细胞相比,SOM中间神经元在GABA A受体介导的突触活动期间仅接受45%的相位电荷转移。总之,我们的研究表明,SOM中间神经元接受相对较弱的抑制性输入,并且不能受到紧张性抑制的影响。

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