Cortical up state activity is enhanced after seizures: a quantitative analysis.
Cortical up state activity is enhanced after seizures: a quantitative analysis.
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癫痫发作后皮质UP状态活性得到增强：定量分析。
DOI：
10.1097/wnp.0b013e3181fdf8bd
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Barth AL
中科院分区：
文献类型：
--
作者：
Gerkin RC;Clem RL;Shruti S;Kass RE;Barth AL
在新皮层中，神经元在静止清醒、慢波睡眠和全身麻醉期间参与活动升高的时期或向上状态。在Up状态期间和之间的放电调节是非常有趣的，因为它可以反映网络内神经元的潜在连通性和兴奋性。在不同的实验和条件下自动分析Up状态发射的开始和特征需要一种鲁棒和准确的Up状态检测方法。作者已经开发了这样一种方法，使用从对照和癫痫发作后组织的神经元全细胞记录中计算的膜电位平均值和方差的测量。这种定量和自动化的方法独立于细胞或条件依赖性的潜在噪声或强直性放电活动的可变性。使用这种方法，作者发现在化学惊厥诱导癫痫发作24小时后，2/3层新皮质神经元的Up状态频率和放电率显著增加。癫痫发作后组织的下降状态表现出更大的膜电位差异，其特征是突触活动增加。先前，作者发现癫痫发作后兴奋性的增加与BK通道的功能获得有关，体外和体内阻断BK通道可以降低兴奋性并消除癫痫发作。因此，作者还评估了bk通道拮抗剂对对照和癫痫发作后神经元Up状态特性的影响。这些数据为Up状态检测和分析建立了一个强大且广泛适用的算法，提供了先前癫痫发作如何增加皮层网络自发放电活动的定量描述，并显示了bk通道拮抗剂如何减少这种异常活动。
In the neocortex, neurons participate in epochs of elevated activity, or Up states, during periods of quiescent wakefulness, slow-wave sleep, and general anesthesia. The regulation of firing during and between Up states is of great interest because it can reflect the underlying connectivity and excitability of neurons within the network. Automated analysis of the onset and characteristics of Up state firing across different experiments and conditions requires a robust and accurate method for Up state detection. Using measurements of membrane potential mean and variance calculated from whole-cell recordings of neurons from control and postseizure tissue, the authors have developed such a method. This quantitative and automated method is independent of cell- or condition-dependent variability in underlying noise or tonic firing activity. Using this approach, the authors show that Up state frequency and firing rates are significantly increased in layer 2/3 neocortical neurons 24 hours after chemo-convulsant-induced seizure. Down states in postseizure tissue show greater membrane-potential variance characterized by increased synaptic activity. Previously, the authors have found that postseizure increase in excitability is linked to a gain-of-function in BK channels, and blocking BK channels in vitro and in vivo can decrease excitability and eliminate seizures. Thus, the authors also assessed the effect of BK-channel antagonists on Up state properties in control and postseizure neurons. These data establish a robust and broadly applicable algorithm for Up state detection and analysis, provide a quantitative description of how prior seizures increase spontaneous firing activity in cortical networks, and show how BK-channel antagonists reduce this abnormal activity.