Two types of nicotinic receptors mediate an excitation of neocortical layer I interneurons
Two types of nicotinic receptors mediate an excitation of neocortical layer I interneurons
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DOI：
10.1152/jn.2002.88.3.1318
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发表时间：
2002-09-01
影响因子：
2.5
通讯作者：
Audinat, E
中科院分区：
文献类型：
--
作者：
Christophe, E;Roebuck, A;Audinat, E
烟碱型乙酰胆碱受体广泛表达于大脑皮层，但其功能作用仍不清楚。在这里，我们研究了烟碱受体激活对I层中间神经元的影响，I层中间神经元含有高密度的胆碱能纤维末梢。在大鼠急性切片中记录的101个神经元中有97个神经元通过烟碱激动剂、乙酰胆碱（500 μ M）、1，1-二甲基-4-苯基哌嗪（500 μ M）或胆碱（10 mM）的局部压力应用而兴奋。生物胞素标记证实，我们的样品包括不同形态类型的第一层中间神经元。烟碱受体激动剂的反应持续存在的谷氨酸和毒蕈碱受体拮抗剂，并进一步添加镉或河豚毒素，表明它们介导的突触后烟碱受体的直接激活。电流的动力学和它们对烟碱受体拮抗剂甲基甘草次酸（1-10 nM）或二氢-β-赤藓定（500 nM）的敏感性表明，反应的早期和晚期成分由α 7和非α 7型受体介导。这两种成分都有内向整流I-V曲线，当细胞内精胺被省略时，这两种曲线不同。单细胞RT-PCR实验鉴定出α 4、α 7和β 2为主要表达的mRNA，表明受体由α 7同聚体和α 4 β 2异聚体组成。最后，选择性兴奋层I interneurons通过激活其烟碱受体导致河豚毒素敏感性增加的抑制性突触电流记录在nonpyramidal细胞，但不是在锥体细胞层II/III。这些结果表明，在I层释放的乙酰胆碱可能会引起通过激活I层中间神经元表达的烟碱受体的皮层网络的抑制解除。
Nicotinic acetylcholine receptors are widely expressed in the neocortex but their functional roles remain largely unknown. Here we investigated the effect of nicotinic receptor activation on interneurons of layer I, which contains a high density of cholinergic fiber terminals. Ninety-seven of 101 neurons recorded in whole cell configuration in rat acute slices were excited by local pressure application of nicotinic agonists, acetylcholine (500 muM), 1,1-dimethyl-4-phenyl-piperazinium (500 muM) or choline (10 mM). Biocytin labeling confirmed that our sample included different morphological types of layer I interneurons. The responses to nicotinic agonists persisted in presence of glutamate and muscarinic receptor antagonists and on further addition of Cd2+ or tetrodotoxin, indicating that they were mediated by direct activation of postsynaptic nicotinic receptors. The kinetics of the currents and their sensitivity to nicotinic receptor antagonists, methyllycaconitine (1-10 nM) or dihydro-beta-erythroidine (500 nM), suggested that early and late components of the responses were mediated by alpha7 and non-alpha7 types of receptors. Both components had inwardly rectifying I-V curves, which differed when intracellular spermine was omitted. Single-cell RT-PCR experiments identified alpha4, alpha7, and beta2 as the predominantly expressed mRNAs, suggesting that the receptors consisted of alpha7 homomers and alpha4beta2 heteromers. Finally, selective excitation of layer I interneurons through activation of their nicotinic receptors resulted in a tetrodotoxin-sensitive increase of inhibitory synaptic currents recorded in nonpyramidal cells but not in pyramidal cells of layer II/III. These results suggest that acetylcholine released in layer I may induce a disinhibition of the cortical network through activation of nicotinic receptors expressed by layer I interneurons.