Yang K-H, Franaszczuk Piotr J, Bergey Gregory K
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Biol Cybern. 2005 Feb;92(2):71-81. doi: 10.1007/s00422-004-0532-0. Epub 2004 Dec 21.
Generation of epileptiform activity typically results from a change in the balance between network excitation and inhibition. Experimental evidence indicates that alterations of either synaptic activity or intrinsic membrane properties can produce increased network excitation. The slow Ca(2+)-activated K(+) currents (sI(AHP)) are important modulators of neuronal firing rate and excitability and have important established and potential roles in epileptogenesis. While the effects of changes in sI(AHP) on individual neuronal excitability are readily studied and well established, the effects of such changes on network behavior are less well known. The experiments here utilize a defined small network model of multicompartment pyramidal cells and an inhibitory interneuron to study the effects of changes in sI(AHP) on network behavior. The benefits of this model system include the ability to observe activity in all cells in a network and the effects of interactions of multiple simultaneous influences. In the model with no inhibitory interneuron, increasing sI(AHP) results in progressively decreasing burst activity. Adding an inhibitory interneuron changes the observed effects; at modest inhibitory strengths, increasing sI(AHP) in all network neurons actually results in increased network bursting (except at very high values). The duration of the burst activity is influenced by the length of delay in a feedback loop, with longer loops resulting in more prolonged bursting. These observations illustrate that the study of potential antiepileptogenic membrane effects must be extended to realistic networks. Network inhibition can dramatically alter the observations seen in pure excitatory networks.
癫痫样活动的产生通常源于网络兴奋与抑制之间平衡的改变。实验证据表明，突触活动或内在膜特性的改变均可导致网络兴奋增加。缓慢的钙激活钾电流（sI(AHP)）是神经元放电频率和兴奋性的重要调节因子，在癫痫发生过程中已确立了重要作用并具有潜在作用。虽然sI(AHP)变化对单个神经元兴奋性的影响易于研究且已得到充分证实，但此类变化对网络行为的影响却鲜为人知。本文的实验利用一个由多室锥体细胞和一个抑制性中间神经元组成的特定小型网络模型，来研究sI(AHP)变化对网络行为的影响。该模型系统的优点包括能够观察网络中所有细胞的活动以及多种同时作用的相互影响的效果。在没有抑制性中间神经元的模型中，增加sI(AHP)会导致爆发活动逐渐减少。添加抑制性中间神经元会改变观察到的效果；在适度的抑制强度下，增加所有网络神经元中的sI(AHP)实际上会导致网络爆发增加（非常高的值除外）。爆发活动的持续时间受反馈回路中延迟长度的影响，回路越长，爆发持续时间越长。这些观察结果表明，对潜在抗癫痫膜效应的研究必须扩展到真实的网络。网络抑制可显著改变在纯兴奋性网络中观察到的结果。
