Spontaneous seizures in Kcna1-null mice lacking voltage-gated Kv1.1 channels activate Fos expression in select limbic circuits.
Spontaneous seizures in Kcna1-null mice lacking voltage-gated Kv1.1 channels activate Fos expression in select limbic circuits.
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DOI：
10.1111/jnc.13206
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发表时间：
2015-10
影响因子：
4.7
通讯作者：
Glasscock E
中科院分区：
文献类型：
--
作者：
Gautier NM;Glasscock E
由于knal基因缺失导致小鼠缺乏电压门控Kv1.1通道，这是一种广泛使用的人类癫痫和癫痫猝死的遗传模型，因为它们频繁发作，基因型-表型与人类相似。癫痫行为、电生理记录和基因表达研究表明，在kcna1缺失的小鼠中，边缘回路对癫痫至关重要，但癫痫发作的确切大脑网络仍不清楚。在这项研究中，通过比较kcna1缺失小鼠的癫痫和非癫痫敲除与野生型对照，使用Fos蛋白表达模式来绘制在基线和自发癫痫发作期间神经元活动增加的边缘脑区域。除了齿状回颗粒细胞层中Fos阳性细胞显著减少外，与野生型相比，非癫痫基因敲除小鼠的所有脑区基本Fos水平没有变化。癫痫发作后，kcna1缺失的大脑在基底外侧杏仁核和齿状门区显示出显著增加的Fos标记，但在海马形成的其他主要细胞层中没有。癫痫发作后杏仁核中Fos的选择性激活表明，kcna1缺失小鼠的额外海马边缘回路可能与癫痫发作的产生或扩散有重要关系。
Mice lacking voltage-gated Kv1.1 channels as a result of deletion of the Kcnal gene are an extensively utilized genetic model of human epilepsy and sudden unexpected death in epilepsy because of their frequent seizures and genotypic-phenotypic similarity to the human condition. Ictal behaviors, electrophysiological recordings, and gene expression studies suggest limbic circuits are critical for epilepsy in Kcna1-null mice, but the exact brain networks recruited by seizures remain unknown. In this study, Fos protein expression patterns were used to map limbic brain regions with increased neuronal activity at baseline and during spontaneous seizures in Kcna1-null mice by comparing seizing and non-seizing knockouts and wild-type controls. Basal Fos levels were unchanged in non-seizing knockout mice compared to wild types for all brain regions examined except the dentate gyrus granule cell layer which exhibited a significant decrease in Fos-positive cells. Following seizures, Kcna1-null brains exhibited significantly increased Fos labeling in the basolateral amygdala and the dentate hilus region, but not in other principal cell layers of the hippocampal formation. The selective Fos activation in the amygdala following seizures suggests that extra hippocampal limbic circuits may be critically involved with seizure generation or spread in Kcna1-null mice.
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DOI：
10.1523/jneurosci.3191-12.2013
发表时间：
2013-01-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Holth JK;Bomben VC;Reed JG;Inoue T;Younkin L;Younkin SG;Pautler RG;Botas J;Noebels JL
通讯作者：
Noebels JL
影响因子：
4.2
作者：
Bomben V;Holth J;Reed J;Cramer P;Landreth G;Noebels J
通讯作者：
Noebels J
影响因子：
5.3
作者：
GODDARD, GV;MCINTYRE, DC;LEECH, CK
通讯作者：
LEECH, CK
影响因子：
5.6
作者：
Klassen TL;Bomben VC;Patel A;Drabek J;Chen TT;Gu W;Zhang F;Chapman K;Lupski JR;Noebels JL;Goldman AM
通讯作者：
Goldman AM
影响因子：
3.4
作者：
Diez, M;Schweinhardt, P;Spenger, C
通讯作者：
Spenger, C