Gap junctions and epileptic seizures--two sides of the same coin?
Gap junctions and epileptic seizures--two sides of the same coin?
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DOI：
10.1371/journal.pone.0020572
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bazhenov M
中科院分区：
文献类型：
--
作者：
Volman V;Perc M;Bazhenov M
电突触（缝隙连接）在神经元集群的同步化中起着关键作用，这也使它们可能成为病理性大脑活动的促进因素。尽管大量实验数据和理论思考表明，通过电突触连接神经元会促进同步活动（因此可能具有致癫痫性），但一些近期的证据对缝隙连接是纯粹致癫痫因素这一假设提出了质疑。特别是，经常发现实验性诱发癫痫发作后神经元间缝隙连接的表达比发作前更高。在此，我们使用一种计算建模方法来探讨神经元缝隙连接在塑造网络对通常与癫痫发作相关的扰动的稳定性方面的作用。我们表明，在某些情况下，添加缝隙连接可以提高网络的动态稳定性，从而抑制与癫痫发作相关的集体电活动。这意味着实验中观察到的癫痫发作后缝隙连接的增加可能有助于防止病情进一步恶化，进一步表明它们是神经元网络对病理活动的适应性反应的结果。然而，如果癫痫发作强烈且持续，我们的模型预测存在一个临界转折点，在该点之后，额外的缝隙连接不再抑制而是强烈促进癫痫发作的加剧。因此，我们的结果揭示了电耦合在癫痫样事件中的复杂作用。网络最终采用哪种动态情况（癫痫发作抑制还是发作加剧）关键取决于癫痫发作的强度和持续时间，这反过来强调了在将缝隙连接与癫痫联系起来时考虑时间和因果方面的重要性。
Electrical synapses (gap junctions) play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity. Although large body of experimental data and theoretical considerations indicate that coupling neurons by electrical synapses promotes synchronous activity (and thus is potentially epileptogenic), some recent evidence questions the hypothesis of gap junctions being among purely epileptogenic factors. In particular, an expression of inter-neuronal gap junctions is often found to be higher after the experimentally induced seizures than before. Here we used a computational modeling approach to address the role of neuronal gap junctions in shaping the stability of a network to perturbations that are often associated with the onset of epileptic seizures. We show that under some circumstances, the addition of gap junctions can increase the dynamical stability of a network and thus suppress the collective electrical activity associated with seizures. This implies that the experimentally observed post-seizure additions of gap junctions could serve to prevent further escalations, suggesting furthermore that they are a consequence of an adaptive response of the neuronal network to the pathological activity. However, if the seizures are strong and persistent, our model predicts the existence of a critical tipping point after which additional gap junctions no longer suppress but strongly facilitate the escalation of epileptic seizures. Our results thus reveal a complex role of electrical coupling in relation to epileptiform events. Which dynamic scenario (seizure suppression or seizure escalation) is ultimately adopted by the network depends critically on the strength and duration of seizures, in turn emphasizing the importance of temporal and causal aspects when linking gap junctions with epilepsy.
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影响因子：
16.2
作者：
Hormuzdi, SG;Pais, I;Monyer, H
通讯作者：
Monyer, H
DOI：
10.1073/pnas.0406343101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Kopell, N;Ermentrout, B
通讯作者：
Ermentrout, B
影响因子：
2.5
作者：
GUTNICK, MJ;CONNORS, BW;PRINCE, DA
通讯作者：
PRINCE, DA
影响因子：
56.9
作者：
DICHTER, MA;AYALA, GF
通讯作者：
AYALA, GF
影响因子：
56.9
作者：
KEPLER, TB;MARDER, E;ABBOTT, LF
通讯作者：
ABBOTT, LF