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首页> 外文期刊>Frontiers in Cellular Neuroscience >Differential modulation of repetitive firing and synchronous network activity in neocortical interneurons by inhibition of A-type K + channels and I h
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Differential modulation of repetitive firing and synchronous network activity in neocortical interneurons by inhibition of A-type K + channels and I h

机译:通过抑制A型K + 通道和I h 来调节新皮层中枢神经元的重复激发和同步网络活动

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摘要

GABAergic interneurons provide the main source of inhibition in the neocortex and are important in regulating neocortical network activity. In the presence 4-aminopyridine (4-AP), CNQX, and D-APV, large amplitude GABA_(A)-receptor mediated depolarizing responses were observed in the neocortex. GABAergic networks are comprised of several types of interneurons, each with its own protein expression pattern, firing properties, and inhibitory role in network activity. Voltage-gated ion channels, especially A-type K~(+)channels, differentially regulate passive membrane properties, action potential (AP) waveform, and repetitive firing properties in interneurons depending on their composition and localization. HCN channels are known modulators of pyramidal cell intrinsic excitability and excitatory network activity. Little information is available regarding how HCN channels functionally modulate excitability of individual interneurons and inhibitory networks. In this study, we examined the effect of 4-AP on intrinsic excitability of fast-spiking basket cells (FS-BCs) and Martinotti cells (MCs). 4-AP increased the duration of APs in both FS-BCs and MCs. The repetitive firing properties of MCs were differentially affected compared to FS-BCs. We also examined the effect of I_(h)inhibition on synchronous GABAergic depolarizations and synaptic integration of depolarizing IPSPs. ZD 7288 enhanced the amplitude and area of evoked GABAergic responses in both cell types. Similarly, the frequency and area of spontaneous GABAergic depolarizations in both FS-BCs and MCs were increased in presence of ZD 7288. Synaptic integration of IPSPs in MCs was significantly enhanced, but remained unaltered in FS-BCs. These results indicate that 4-AP differentially alters the firing properties of interneurons, suggesting MCs and FS-BCs may have unique roles in GABAergic network synchronization. Enhancement of GABAergic network synchronization by ZD 7288 suggests that HCN channels attenuate inhibitory network activity.
机译:GABA能神经元提供了新皮层抑制的主要来源,并且在调节新皮层网络活动中很重要。在存在4-氨基吡啶(4-AP),CNQX和D-APV的情况下,在新皮层中观察到大幅度的GABA_(A)-受体介导的去极化反应。 GABA能网络由几种类型的中间神经组成,每种中间神经都有自己的蛋白质表达模式,放电特性和对网络活动的抑制作用。电压门控离子通道,特别是A型K〜(+)通道,根据中间神经元的组成和位置,差异地调节被动膜的特性,动作电位(AP)波形和重复发射特性。 HCN通道是锥体细胞固有兴奋性和兴奋性网络活动的已知调节剂。关于HCN通道如何在功能上调节单个中间神经元和抑制​​网络的兴奋性的信息很少。在这项研究中,我们检查了4-AP对快速加料篮细胞(FS-BCs)和马蒂诺蒂(MCs)内在兴奋性的影响。 4-AP增加了FS-BC和MC中AP的持续时间。与FS-BC相比,MC的重复发射特性受到不同的影响。我们还检查了I_(h)抑制对同步GABA能性去极化和去极化IPSPs突触整合的影响。 ZD 7288增强了两种细胞类型中诱发的GABA能反应的幅度和面积。同样,在ZD 7288的存在下,FS-BCs和MCs中自发GABA能去极化的频率和面积也增加。IPSPs在MCs中的突触整合显着增强,但在FS-BCs中保持不变。这些结果表明4-AP差异性地改变了中间神经元的放电特性,表明MC和FS-BC在GABA能网络同步中可能具有独特的作用。 ZD 7288增强GABA能网络同步性表明,HCN通道减弱了抑制性网络活动。

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