Gap junctions modulate seizures in a mean-field model of general anesthesia for the cortex
Gap junctions modulate seizures in a mean-field model of general anesthesia for the cortex
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DOI：
10.1007/s11571-012-9194-0
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发表时间：
2012-06-01
影响因子：
3.7
通讯作者：
Sleigh, Jamie W.
中科院分区：
文献类型：
--
作者：
Steyn-Ross, Moira L.;Steyn-Ross, D. Alistair;Sleigh, Jamie W.
在慢波睡眠、全身麻醉和全身性癫痫发作时，患者意识缺失。这些状态在头皮脑电图上表现为低频大振幅行波。因此，振荡状态可能是未能形成意识所必需的连贯神经元集合的迹象。全身性癫痫发作是一种病理脑状态，是同步神经元活动波的最明显表现。由于间隙连接提供相邻神经元之间的直接电连接，从而增强同步行为，减少间隙连接的电导应该抑制癫痫发作；然而，没有明确的实验证据证明这一点。在这里，我们报告了一个基于生理学的皮层模型的理论预测，该模型描述了从意识到昏迷的全身麻醉阶段，包括化学突触和直接电紧张突触。模型动力学表现出Hopf（时间）和Turing（空间）不稳定性；Hopf不稳定性对应于慢波睡眠、全身麻醉和癫痫发作时的缓慢振荡状态（小于或接近8hz）。我们认为霍普夫模式和图灵模式之间微妙的平衡相互作用为大脑默认的非认知休息状态提供了一种规范机制。我们证明了由隙结扩散设置的图灵模式通常可以防止进入振荡模式；通过减少间隙传导来削弱图灵模式，可以释放不受控制的Hopf振荡，从而增加癫痫发作的倾向，同时增加对gaba能麻醉的敏感性。
During slow-wave sleep, general anesthesia, and generalized seizures, there is an absence of consciousness. These states are characterized by low-frequency large-amplitude traveling waves in scalp electroencephalogram. Therefore the oscillatory state might be an indication of failure to form coherent neuronal assemblies necessary for consciousness. A generalized seizure event is a pathological brain state that is the clearest manifestation of waves of synchronized neuronal activity. Since gap junctions provide a direct electrical connection between adjoining neurons, thus enhancing synchronous behavior, reducing gap-junction conductance should suppress seizures; however there is no clear experimental evidence for this. Here we report theoretical predictions for a physiologically-based cortical model that describes the general anesthetic phase transition from consciousness to coma, and includes both chemical synaptic and direct electrotonic synapses. The model dynamics exhibits both Hopf (temporal) and Turing (spatial) instabilities; the Hopf instability corresponds to the slow (less than or similar to 8 Hz) oscillatory states similar to those seen in slow-wave sleep, general anesthesia, and seizures. We argue that a delicately balanced interplay between Hopf and Turing modes provides a canonical mechanism for the default non-cognitive rest state of the brain. We show that the Turing mode, set by gap-junction diffusion, is generally protective against entering oscillatory modes; and that weakening the Turing mode by reducing gap conduction can release an uncontrolled Hopf oscillation and hence an increased propensity for seizure and simultaneously an increased sensitivity to GABAergic anesthesia.