GABAA receptor-mediated tonic inhibition in thalamic neurons
GABAA receptor-mediated tonic inhibition in thalamic neurons
复制标题
DOI：
10.1523/jneurosci.3362-05.2005
复制
发表时间：
2005-12-14
影响因子：
5.3
通讯作者：
Crunelli, V
中科院分区：
文献类型：
--
作者：
Cope, DW;Hughes, SW;Crunelli, V
强直性GABA(A)受体介导的抑制通常是由含有δ亚基的突触外受体产生的。由于delta亚基在丘脑中高度表达，我们测试了背外侧膝状核（dLGN）和腹底复合体的丘脑皮质（TC）神经元是否表现出强直抑制。加巴嗪（GBZ） （50 μ M）的局部应用显示，75%和63%的TC神经元分别从两个核中存在20 pA的紧张电流。丘脑网状核（NRT） gaba能神经元未见强直电流。1 μ M GABA在100%的TC神经元中使强直电流幅值增加到接近70 pA，但在NRT神经元中仍未观察到。在dLGN TC神经元中，强直电流对低浓度的δ亚单位特异性受体激动剂异四氢脱氧皮质酮（100 nM）和4,5,6,7-四氢异恶唑[5,4-c]-吡啶-3-醇（THIP） （100 nM）敏感，但对苯二氮卓类氟拉西泮（5 μ M）不敏感。低浓度的GBZ （25-200 nM）优先阻断强直电流，而主要维持相突触抑制。在细胞内电流箝位条件下，强压电流与GBZ的优先阻断导致了小的去极化和输入电阻的增加。通过细胞外单单元记录，强直电流的阻断导致低阈值爆发放电的停止和强直放电的促进。THIP超极化TC神经元增强强直电流并促进突发放电。因此，TC神经元中的强直电流产生抑制性张力。它的调节有助于不同放电模式之间的转换，促进不同行为状态之间的转换，并易导致失神发作。
Tonic GABA(A) receptor-mediated inhibition is typically generated by delta subunit-containing extrasynaptic receptors. Because the delta subunit is highly expressed in the thalamus, we tested whether thalamocortical (TC) neurons of the dorsal lateral geniculate nucleus (dLGN) and ventrobasal complex exhibit tonic inhibition. Focal application of gabazine (GBZ) (50 mu M) revealed the presence of a 20 pA tonic current in 75 and 63% of TC neurons from both nuclei, respectively. No tonic current was observed in GABAergic neurons of the nucleus reticularis thalami (NRT). Bath application of 1 mu M GABA increased tonic current amplitude to similar to 70 pA in 100% of TC neurons, but it was still not observed in NRT neurons. In dLGN TC neurons, the tonic current was sensitive to low concentrations of the delta subunit-specific receptor agonists allotetrahydrodeoxycorticosterone (100 nM) and 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) (100 nM) but insensitive to the benzodiazepine flurazepam (5 mu M). Bath application of low concentrations of GBZ (25-200 nM) preferentially blocked the tonic current, whereas phasic synaptic inhibition was primarily maintained. Under intracellular current-clamp conditions, the preferential block of the tonic current with GBZ led to a small depolarization and increase in input resistance. Using extracellular single-unit recordings, block of the tonic current caused the cessation of low-threshold burst firing and promoted tonic firing. Enhancement of the tonic current by THIP hyperpolarized TC neurons and promoted burst firing. Thus, tonic current in TC neurons generates an inhibitory tone. Its modulation contributes to the shift between different firing modes, promotes the transition between different behavioral states, and predisposes to absence seizures.