Excitatory actions of GABA in the suprachiasmatic nucleus
Excitatory actions of GABA in the suprachiasmatic nucleus
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DOI：
10.1523/jneurosci.5750-07.2008
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发表时间：
2008-05-21
影响因子：
5.3
通讯作者：
Kim, Yang In
中科院分区：
文献类型：
--
作者：
Choi, Hee Joo;Lee, C. Justin;Kim, Yang In
视交叉上核（SCN）中的神经元负责产生昼夜节律振荡，了解这些神经元如何通信以形成功能回路是一个关键问题。神经递质GABA及其受体在SCN中广泛表达，它们在SCN中介导细胞间的通讯。以前的研究已经提出了GABA在白天可以作为成年SCN神经元中的兴奋性递质的可能性，但这项工作是有争议的。在本研究中，我们首先测试的假设，GABA可以引起兴奋性反应，在某些阶段的日常周期广泛采样SCN神经元如何响应GABA细胞外单单位记录和短杆菌肽穿孔补丁记录技术。我们发现，虽然GABA抑制大多数SCN神经元，但无论何时，SCN的背侧和腹侧区域都存在一定水平的GABA介导的兴奋。这些GABA诱发的兴奋性反应是最常见的在夜间在背侧SCN区域。Na+-K+-2Cl（-）协同转运蛋白（NKCC）抑制剂布美他尼可阻止这些兴奋性反应。在单个神经元中，布美他尼的应用足以将GABA诱发的兴奋改变为抑制。钙成像实验还表明，GABA引起的SCN细胞中的钙瞬变高度依赖于NKCC亚型1（NKCC 1）。最后，Western blot分析表明，NKCC 1在背侧SCN中的表达在夜间较高。总之，这项工作表明，GABA可以在成年SCN神经元之间的通信中发挥兴奋作用，并且这种兴奋严重依赖于NKCC 1。
Neurons in the suprachiasmatic nucleus (SCN) are responsible for the generation of circadian oscillations, and understanding how these neurons communicate to form a functional circuit is a critical issue. The neurotransmitter GABA and its receptors are widely expressed in the SCN where they mediate cell-to-cell communication. Previous studies have raised the possibility that GABA can function as an excitatory transmitter in adult SCN neurons during the day, but this work is controversial. In the present study, we first tested the hypothesis that GABA can evoke excitatory responses during certain phases of the daily cycle by broadly sampling how SCN neurons respond to GABA using extracellular single-unit recording and gramicidin-perforated-patch recording techniques. We found that, although GABA inhibits most SCN neurons, some level of GABA-mediated excitation was present in both dorsal and ventral regions of the SCN, regardless of the time of day. These GABA-evoked excitatory responses were most common during the night in the dorsal SCN region. The Na+-K+-2Cl(-) cotransporter (NKCC) inhibitor, bumetanide, prevented these excitatory responses. In individual neurons, the application of bumetanide was sufficient to change GABA-evoked excitation to inhibition. Calcium-imaging experiments also indicated that GABA-elicited calcium transients in SCN cells are highly dependent on the NKCC isoform 1 (NKCC1). Finally, Western blot analysis indicated that NKCC1 expression in the dorsal SCN is higher in the night. Together, this work indicates that GABA can play an excitatory role in communication between adult SCN neurons and that this excitation is critically dependent on NKCC1.