Aston University, Birmingham B4 7ET, UK.
Eur J Neurosci. 2011 Apr;33(8):1471-82. doi: 10.1111/j.1460-9568.2011.07645.x. Epub 2011 Mar 13.
The rodent ventrobasal (VB) thalamus contains a relatively uniform population of thalamocortical (TC) neurons that receive glutamatergic input from the vibrissae and the somatosensory cortex, and inhibitory input from the nucleus reticularis thalami (nRT). In this study we describe γ-aminobutyric acid (GABA)(A) receptor-dependent slow outward currents (SOCs) in TC neurons that are distinct from fast inhibitory postsynaptic currents (IPSCs) and tonic currents. SOCs occurred spontaneously or could be evoked by hypo-osmotic stimulus, and were not blocked by tetrodotoxin, removal of extracellular Ca(2+) or bafilomycin A1, indicating a non-synaptic, non-vesicular GABA origin. SOCs were more common in TC neurons of the VB compared with the dorsal lateral geniculate nucleus, and were rarely observed in nRT neurons, whilst SOC frequency in the VB increased with age. Application of THIP, a selective agonist at δ-subunit-containing GABA(A) receptors, occluded SOCs, whereas the benzodiazepine site inverse agonist β-CCB had no effect, but did inhibit spontaneous and evoked IPSCs. In addition, the occurrence of SOCs was reduced in mice lacking the δ-subunit, and their kinetics were also altered. The anti-epileptic drug vigabatrin increased SOC frequency in a time-dependent manner, but this effect was not due to reversal of GABA transporters. Together, these data indicate that SOCs in TC neurons arise from astrocytic GABA release, and are mediated by δ-subunit-containing GABA(A) receptors. Furthermore, these findings suggest that the therapeutic action of vigabatrin may occur through the augmentation of this astrocyte-neuron interaction, and highlight the importance of glial cells in CNS (patho) physiology.
啮齿动物腹侧基底（VB）丘脑包含相对均匀的丘脑皮质（TC）神经元群体，这些神经元接收来自触须和躯体感觉皮层的谷氨酸能输入，以及来自丘脑网状核（nRT）的抑制性输入。在这项研究中，我们描述了 TC 神经元中γ-氨基丁酸（GABA）（A）受体依赖性的缓慢外向电流（SOCs），这些电流与快速抑制性突触后电流（IPSCs）和紧张性电流不同。SOCs 可以自发发生，也可以通过低渗刺激诱发，并且不受河豚毒素、细胞外 Ca(2+)去除或巴弗洛霉素 A1 的阻断，表明 SOCs 具有非突触、非囊泡 GABA 起源。SOCs 在 VB 中的 TC 神经元中比在背外侧膝状体核中更为常见，而在 nRT 神经元中很少观察到，而 VB 中的 SOC 频率随着年龄的增长而增加。THIP 的应用，一种 δ 亚基包含的 GABA(A)受体的选择性激动剂，封闭了 SOCs，而苯二氮䓬结合位点的反向激动剂 β-CCB 没有影响，但确实抑制了自发性和诱发的 IPSCs。此外，缺乏 δ 亚基的小鼠中 SOCs 的发生减少，其动力学也发生改变。抗癫痫药物 vigabatrin 以时间依赖性方式增加 SOC 频率，但这种作用不是由于 GABA 转运体的逆转。总之，这些数据表明，TC 神经元中的 SOCs 源自星形胶质细胞 GABA 的释放，并由 δ 亚基包含的 GABA(A)受体介导。此外，这些发现表明 vigabatrin 的治疗作用可能是通过增强这种星形胶质细胞-神经元相互作用而发生的，并强调了胶质细胞在中枢神经系统（病理）生理学中的重要性。
