Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells
Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells
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DOI：
10.1152/jn.2002.87.5.2624
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发表时间：
2002-05-01
影响因子：
2.5
通讯作者：
Mody, I
中科院分区：
文献类型：
--
作者：
Nusser, Z;Mody, I
在某些神经细胞中，GABA激活GABA(A)受体会导致时相和紧张性电导。突触受体的短暂激活会产生相性抑制，而紧张性抑制源于GABA对突触外受体的作用，如小脑颗粒细胞，在小脑颗粒细胞中，它被认为是由具有特定亚单位组成(α(6)β(X)Delta)的突触外GABA(A)受体激活的结果。在这里，我们表明，在成年大鼠海马片，细胞外GABA水平足够高，以产生强大的紧张性抑制增量亚单位表达齿状回颗粒细胞。在这些细胞中，平均紧张性电流大约是自发性突触电流产生的四倍，频率类似于10赫兹。用NO-711(2.5微米)拮抗GABA转运体GAT-1，在不影响时相成分的情况下，选择性地增强了330%的紧张性抑制。相反，通过延长抑制性突触后电流(IPSCs)的衰减，苯二氮卓类激动剂唑吡坦(0.5um)使时相抑制增加66%，而平均紧张性电导保持不变。这些结果表明，在体外切片制备中，成年大鼠齿状回颗粒细胞可记录到一种紧张性GABA(A)受体介导的电导。此外，我们已经确定了不同的药理学工具来选择性地修改紧张性和相性抑制，使未来的研究能够探索它们在神经元功能中的具体作用。
In some nerve cells, activation of GABA(A) receptors by GABA results in phasic and tonic conductances. Transient activation of synaptic receptors generates phasic inhibition, whereas tonic inhibition originates from GABA acting on extrasynaptic receptors, like in cerebellar granule cells, where it is thought to result from the activation of extrasynaptic GABA(A) receptors with a specific subunit composition (alpha(6)beta(x)delta). Here we show that in adult rat hippocampal slices, extracellular GABA levels are sufficiently high to generate a powerful tonic inhibition in delta subunit-expressing dentate gyrus granule cells. In these cells, the mean tonic current is approximately four times larger than that produced by spontaneous synaptic currents occurring at a frequency of similar to10 Hz. Antagonizing the GABA transporter GAT-1 with NO-711 (2.5 muM) selectively enhanced tonic inhibition by 330% without affecting the phasic component. In contrast, by prolonging the decay of inhibitory postsynaptic currents (IPSCs), the benzodiazepine agonist zolpidem (0.5 muM) augmented phasic inhibition by 66%, while leaving the mean tonic conductance unchanged. These results demonstrate that a tonic GABA(A) receptor-mediated conductance can be recorded from dentate gyrus granule cells of adult rats in in vitro slice preparations. Furthermore, we have identified distinct pharmacological tools to selectively modify tonic and phasic inhibitions, allowing future studies to investigate their specific roles in neuronal function.