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Kv2.1 Potassium Channels Regulate Repetitive Burst Firing in Extratelencephalic Neocortical Pyramidal Neurons
Cerebral Cortex ( IF 2.9 ) Pub Date : 2021-07-20 , DOI: 10.1093/cercor/bhab266
Greg S Newkirk 1 , Dongxu Guan 2 , Nikolai Dembrow 1, 3 , William E Armstrong 2 , Robert C Foehring 2 , William J Spain 1, 3
Affiliation  

Coincidence detection and cortical rhythmicity are both greatly influenced by neurons’ propensity to fire bursts of action potentials. In the neocortex, repetitive burst firing can also initiate abnormal neocortical rhythmicity (including epilepsy). Bursts are generated by inward currents that underlie a fast afterdepolarization (fADP) but less is known about outward currents that regulate bursting. We tested whether Kv2 channels regulate the fADP and burst firing in labeled layer 5 PNs from motor cortex of the Thy1-h mouse. Kv2 block with guangxitoxin-1E (GTx) converted single spike responses evoked by dendritic stimulation into multispike bursts riding on an enhanced fADP. Immunohistochemistry revealed that Thy1-h PNs expressed Kv2.1 (not Kv2.2) channels perisomatically (not in the dendrites). In somatic macropatches, GTx-sensitive current was the largest component of outward current with biophysical properties well-suited for regulating bursting. GTx drove ~40% of Thy1 PNs stimulated with noisy somatic current steps to repetitive burst firing and shifted the maximal frequency-dependent gain. A network model showed that reduction of Kv2-like conductance in a small subset of neurons resulted in repetitive bursting and entrainment of the circuit to seizure-like rhythmic activity. Kv2 channels play a dominant role in regulating onset bursts and preventing repetitive bursting in Thy1 PNs.

中文翻译:

Kv2.1 钾通道调节脑外新皮质锥体神经元的重复爆发

巧合检测和皮层节律性都受到神经元触发动作电位爆发的倾向的极大影响。在新皮质中,重复的爆发性放电也可以引发异常的新皮质节律性(包括癫痫)。爆发是由作为快速后去极化 (fADP) 基础的内向电流产生的,但对于调节爆发的外向电流知之甚少。我们测试了 Kv2 通道是否调节来自 Thy1-h 小鼠运动皮层的标​​记的第 5 层 PNs 中的 fADP 和突发放电。Kv2 块与 guangxitoxin-1E (GTx) 将由树突刺激引起的单尖峰反应转化为增强 fADP 上的多尖峰爆发。免疫组织化学显示 Thy1-h PNs 表达 Kv2.1(不是 Kv2.2)通道 perisomatically(不在树突中)。在体细胞宏补丁中,GTx敏感电流是外向电流的最大组成部分,具有非常适合调节爆发的生物物理特性。GTx 将约 40% 的 Thy1 PN 用嘈杂的体细胞电流步骤刺激到重复的突发发射,并改变了最大频率相关增益。一个网络模型表明,一小部分神经元中 Kv2 样电导的降低导致电路重复爆裂和夹带到癫痫样节律活动。Kv2 通道在调节 Thy1 PNs 的爆发和防止重复爆发中起主导作用。一个网络模型表明,一小部分神经元中 Kv2 样电导的降低导致电路重复爆裂和夹带到癫痫样节律活动。Kv2 通道在调节 Thy1 PNs 的爆发和防止重复爆发中起主导作用。一个网络模型表明,一小部分神经元中 Kv2 样电导的降低导致电路重复爆裂和夹带到癫痫样节律活动。Kv2 通道在调节 Thy1 PNs 的爆发和防止重复爆发中起主导作用。
更新日期:2021-07-20
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