Wang D-G, Gong N, Luo B, Xu T-L
Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Huang-Shan Road, Hefei 230027, Anhui, China.
Neuroscience. 2006 Aug 11;141(1):133-41. doi: 10.1016/j.neuroscience.2006.03.045. Epub 2006 May 3.
Neural inhibition in the brain is mainly mediated by ionotropic GABA type A receptors. Apart from the GABA type A receptors, both K(+)-Cl(-) cotransporter isoform 2 and the GABA-synthesizing enzyme, glutamic acid decarboxylase, are essential determinants for GABA type A receptor-mediated inhibition. By using immunofluorescent staining, we observed that K(+)-Cl(-) cotransporter isoform 2, GABA type A receptor beta2/3 subunits and a presynaptically localized glutamic acid decarboxylase isoform, glutamic acid decarboxylase 65, were all absent in adult Sprague-Dawley rat medial habenular nucleus, while immunopositive staining for glutamic acid decarboxylase 67, GABA and GABA type B receptor type 2 subunit were present in the medial habenular nucleus. Consistent with the lack of GABA type A signaling as detected by immunohistochemistry, GABA (100 muM) evoked no measurable currents in the medial habenular nucleus but induced bicuculline-sensitive currents in the lateral habenular nucleus and in the CA1 area of hippocampus. We also failed to record miniature inhibitory postsynaptic currents in medial habenular nucleus neurons. These results support the idea that GABAergic transmission in medial habenular nucleus is probably not mediated by any of the most common GABA type A receptor subtypes. Our data suggest that GABA type B receptor-mediated inhibition may play a role in balancing neuronal excitation in this special region. Further exploration for factors determining medial habenular nucleus neural inhibition will lead to a more complete understanding of control of synaptic balance in the CNS.
大脑中的神经抑制主要由离子型GABA A受体介导。除了GABA A受体外，K(+)-Cl(-)共转运体亚型2和GABA合成酶谷氨酸脱羧酶都是GABA A受体介导的抑制作用的重要决定因素。通过免疫荧光染色，我们观察到，在成年Sprague-Dawley大鼠内侧缰核中，K(+)-Cl(-)共转运体亚型2、GABA A受体β2/3亚基以及突触前定位的谷氨酸脱羧酶亚型谷氨酸脱羧酶65均不存在，而内侧缰核中存在谷氨酸脱羧酶67、GABA和GABA B受体2型亚基的免疫阳性染色。与免疫组化检测到的GABA A信号缺乏一致，GABA（100 μM）在内侧缰核中未诱发可测量的电流，但在外侧缰核和海马CA1区诱发了荷包牡丹碱敏感电流。我们也未能记录到内侧缰核神经元中的微小抑制性突触后电流。这些结果支持这样一种观点，即内侧缰核中的GABA能传递可能不是由任何最常见的GABA A受体亚型介导的。我们的数据表明，GABA B受体介导的抑制可能在平衡这个特殊区域的神经元兴奋中起作用。对决定内侧缰核神经抑制的因素进行进一步探索将有助于更全面地了解中枢神经系统中突触平衡的控制。
