Action potential initiation in neocortical inhibitory interneurons.
Action potential initiation in neocortical inhibitory interneurons.
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DOI：
10.1371/journal.pbio.1001944
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发表时间：
2014-09
期刊：
影响因子：
9.8
通讯作者：
Shu Y
中科院分区：
文献类型：
--
作者：
Li T;Tian C;Scalmani P;Frassoni C;Mantegazza M;Wang Y;Yang M;Wu S;Shu Y
钠通道增加了抑制性中间神经元的多样性大脑皮层中不同的抑制性中间神经元群表达不同的钠通道亚型，导致不同的动作电位阈值和网络兴奋性。抑制性中间神经元中动作电位（AP）的产生对于皮质兴奋-抑制平衡和信息处理至关重要。然而，目前尚不清楚是什么决定了不同中间神经元中 AP 的启动。我们关注新皮质中两种主要的中间神经元类型：表达小白蛋白（PV）和生长抑素（SST）的神经元。小鼠前额皮质切片的膜片钳记录表明，轴突而非体细胞 Na+ 通道表现出不同的电压依赖性特性。 SST 中轴突通道的最小激活电压远高于 PV 细胞中的（~7 mV），这与 AP 阈值的差异一致。 SST 细胞轴突初始段 (AIS) 处高阈值通道亚型和低阈值通道亚型的更加混合的分布可能导致这些差异。令人惊讶的是，发现 NaV1.2 积聚在 SST 的 AIS 处，而不是 PV 电池处；减少中间神经元中 NaV1.2 介导的电流促进了循环网络活动。总之，我们的结果揭示了中间神经元中轴突 Na+ 通道的分子特性及其对 AP 生成和网络活动调节的贡献。大脑皮层的抑制性中间神经元在许多方面都是多种多样的。在这里，我们检查这种多样性是否延伸到轴突离子通道的组成，这可能决定神经元的兴奋性。我们对从两个转基因小鼠系获得的脑切片中的皮质中间神经元轴突进行了膜片钳记录。在每个小鼠品系中，不同的抑制性中间神经元群体——表达小白蛋白（PV）的神经元或表达生长抑素（SST）的神经元——用绿色荧光蛋白标记以允许可视化。我们发现，两种细胞类型的动作电位均始于轴突初始段（轴突最接近细胞体的特殊区域），但 SST 神经元比 PV 神经元具有更高的动作电位阈值，因为它们的钠通道需要更大程度的去极化才能完全激活。在分子水平上，我们发现SST神经元中的钠通道群需要更大的去极化，因为它具有更混合的高阈值和低阈值钠通道亚型的组成。总之，这项研究揭示了钠通道的分子特性和电压依赖性的多样性，钠通道负责启动不同中间神经元群体的动作电位。此外，抑制性中间神经元中钠通道特定亚型——NaV1.2的存在可能解释了为什么该通道的功能丧失突变会导致癫痫。
Sodium channels add variety to inhibitory interneurons Different populations of inhibitory interneurons in the cerebral cortex express distinct subtypes of sodium channels, resulting in diverse action potential thresholds and network excitability. Action potential (AP) generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing. However, it remains unclear what determines AP initiation in different interneurons. We focused on two predominant interneuron types in neocortex: parvalbumin (PV)- and somatostatin (SST)-expressing neurons. Patch-clamp recording from mouse prefrontal cortical slices showed that axonal but not somatic Na+ channels exhibit different voltage-dependent properties. The minimal activation voltage of axonal channels in SST was substantially higher (∼7 mV) than in PV cells, consistent with differences in AP thresholds. A more mixed distribution of high- and low-threshold channel subtypes at the axon initial segment (AIS) of SST cells may lead to these differences. Surprisingly, NaV1.2 was found accumulated at AIS of SST but not PV cells; reducing NaV1.2-mediated currents in interneurons promoted recurrent network activity. Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity. Inhibitory interneurons in the cerebral cortex are diverse in many respects. Here, we examine whether this diversity extends to the composition of ion channels along the axon, which might determine the neurons' excitability. We performed patch-clamp recordings from cortical interneuron axons in brain slices obtained from two transgenic mouse lines. In each mouse line, distinct populations of inhibitory interneurons—those that express parvalbumin (PV) or those that express somatostatin (SST)—were labeled with green fluorescent protein to allow visualization. We show that action potentials initiate at the axon initial segment (a specialized region of the axon closest to the cell body) in both cell types, but SST neurons have a higher action potential threshold than PV neurons because their sodium channels require a greater degree of depolarization to be fully activated. At the molecular level, we found that the population of sodium channels in SST neurons requires a larger depolarization because it has a more mixed composition of high- and low-threshold sodium channel subtypes. In summary, this study reveals diversity in the molecular identity and voltage dependence of sodium channels that are responsible for initiating action potentials in different populations of interneurons. In addition, the presence of a particular subtype of sodium channel—NaV1.2—in inhibitory interneurons might explain why loss-of-function mutations in this channel result in epilepsy.
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