Activity-dependent ectopic action potentials in regular-spiking neurons of the neocortex.

Activity-dependent ectopic action potentials in regular-spiking neurons of the neocortex.
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DOI:
10.3389/fncel.2023.1267687
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发表时间:
2023
影响因子:
5.3
通讯作者:
--
中科院分区:
医学2区
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动作电位通常沿神经元的轴突从轴突起始段(AIS)向突触前末梢沿着顺向传播。在某些情况下,动作电位在远端位置启动后,也会沿相反方向逆向行进。鉴于它们起始于非典型部位,我们将这些事件称为“异位动作电位”。异位动作电位(EAPs)最初在包括癫痫发作和神经损伤的病理条件下观察到。一些研究已经描述了癫痫发作模型中发射EAP的规则尖峰(RS)锥体神经元。在非病理条件下,EAP在少数神经元群体中被报道,并且我们的小组发现EAP可以在新皮层中大比例的表达小白蛋白的中间神经元中被诱导。然而,据我们所知,在非病理条件下,新皮层中最大的神经元群体,锥体神经元,没有先前的异位放电报告。我们利用全细胞膜片钳技术进行体外记录。为了诱发EAPs,我们用长的、逐渐增加的电流步骤或以3种不同的方式传递的30、60或100 Hz的短脉冲序列触发顺向动作电位,这些方式在刺激和静息期持续时间上不同。我们发现,一个大比例(72.7%)的新皮质RS细胞从小鼠可以在体外特定的刺激后发射EAP,并且大多数RS细胞(56.1%)能够在广泛的刺激条件下发射EAP。在我们能够诱发EAP的37个RS神经元中,在看到第一个EAP之前,在平均约81.4 s的过程中平均传递了863.8个顺向动作电位。我们观察到,一些细胞对特定的刺激频率作出反应,而选择性较低,这表明在一个子集的细胞频率调谐。我们的研究结果表明,锥体细胞可以整合信息在很长的时间尺度之前,短暂地进入一个模式的自我产生的发射,起源于远端轴突。令人惊讶的普遍存在的EAP产生RS细胞提出了有趣的问题异位尖峰信息处理,皮层振荡和癫痫易感性的潜在作用。
Action potentials usually travel orthodromically along a neuron’s axon, from the axon initial segment (AIS) toward the presynaptic terminals. Under some circumstances action potentials also travel in the opposite direction, antidromically, after being initiated at a distal location. Given their initiation at an atypical site, we refer to these events as “ectopic action potentials.” Ectopic action potentials (EAPs) were initially observed in pathological conditions including seizures and nerve injury. Several studies have described regular-spiking (RS) pyramidal neurons firing EAPs in seizure models. Under nonpathological conditions, EAPs were reported in a few populations of neurons, and our group has found that EAPs can be induced in a large proportion of parvalbumin-expressing interneurons in the neocortex. Nevertheless, to our knowledge there have been no prior reports of ectopic firing in the largest population of neurons in the neocortex, pyramidal neurons, under nonpathological conditions. We performed in vitro recordings utilizing the whole-cell patch clamp technique. To elicit EAPs, we triggered orthodromic action potentialswith either long, progressively increasing current steps, or with trains of brief pulses at 30, 60, or 100 Hz delivered in 3 different ways, varying in stimulus and resting period duration. We found that a large proportion (72.7%) of neocortical RS cells from mice can fire EAPs after a specific stimulus in vitro, and that most RS cells (56.1%) are capable of firing EAPs across a broad range of stimulus conditions. Of the 37 RS neurons in which we were able to elicit EAPs, it took an average of 863.8 orthodromic action potentials delivered over the course of an average of ~81.4 s before the first EAP was seen. We observed that some cells responded to specific stimulus frequencies while less selective, suggesting frequency tuning in a subset of the cells. Our findings suggest that pyramidal cells can integrate information over long time-scales before briefly entering a mode of self-generated firing that originates in distal axons. The surprising ubiquity of EAP generation in RS cells raises interesting questions about the potential roles of ectopic spiking in information processing, cortical oscillations, and seizure susceptibility.
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