癫痫发作期间何时以及哪些神经元组同步放电存在不确定性。虽然一些研究发现癫痫发作时的射击不均,其他人建议在癫痫发作核心同步神经元放电。我们测试了癫痫发作期间的神经元活动是否在回路中兴奋性神经元连接的方向上有序。在隔颞层组织的薄片中横向有很强的兴奋性连接,在海马中具有抑制性跨薄片连接,这允许测试连通性假设。我们进一步测试了癫痫发生是否增强了同步性,而抗癫痫药物的使用是否会破坏同步性。我们使用小型微电极阵列记录了CA1锥体神经元的局部场电位,并通过快速,反复海马刺激方案。我们比较了互相关,θ相位同步,熵,和事件同步。这些分析表明,发射模式沿着层状相关,但不是半颞叶,诱发性癫痫发作期间的轴。在点燃期间,神经元同步性沿着板层轴增加,而沿隔膜轴的同步性保持相对较低。此外,theta相分布表明,随着点燃沿层状方向而不是沿层状方向进行,CA1锥体细胞放电优先于theta振荡负峰。最后,事件同步表明,沿着板层轴的神经元放电比沿着隔颞轴的神经元放电更同步。苯妥英和左乙拉西坦治疗后,同步性和相位偏好显着降低。癫痫发作和癫痫发生期间CA1锥体神经元的同步性结构取决于解剖连通性和可塑性。重要声明我们可以通过了解同步性的结构来提高脑刺激治疗癫痫的疗效。电刺激可能通过使神经元去同步来破坏癫痫发作,但是在癫痫发作期间哪些神经元群同步或混乱地放电是不确定的。这里,我们证明了由兴奋性连接连接的神经元在癫痫发作期间同步放电,这种同步性是由癫痫发生和抗癫痫药物调节的。仔细瞄准以破坏同步性的闭环脑刺激可以改善癫痫发作的治疗。
There is uncertainty regarding when and which groups of neurons fire synchronously during seizures. While several studies found heterogeneous firing during seizures, others suggested synchronous neuronal firing in the seizure core. We tested whether neuronal activity during seizures is orderly in the direction of the excitatory neuronal connections in the circuit. There are strong excitatory connections laterally within the septotemporally organized lamella and inhibitory trans-lamellar connections in the hippocampus, which allow testing of the connectivity hypothesis. We further tested whether epileptogenesis enhances synchrony and antiseizure drug administration disrupts it. We recorded local field potentials from CA1 pyramidal neurons using a small microelectrode array and kindled rats by a rapid, recurrent hippocampal stimulation protocol. We compared cross-correlation, theta phase synchronization, entropy, and event synchronization. These analyses revealed that the firing pattern was correlated along the lamellar, but not the
septotemporal, axis during evoked seizures. During kindling, neuronal synchrony increased along the lamellar axis, while synchrony along the
septotemporal axis remained relatively low. Additionally, the theta phase distribution demonstrated that CA1 pyramidal cell firing became preferential for theta oscillation negative peak as kindling progressed in the lamellar direction but not in the trans-lamellar direction. Last, event synchronization demonstrated that neuronal firings along the lamellar axis were more synchronized than those along the
septotemporal axis. There was a marked decrease in synchronization and phase preference after treatment with phenytoin and levetiracetam. The synchrony structure of CA1 pyramidal neurons during seizures and epileptogenesis depends on anatomic connectivity and plasticity.SIGNIFICANCE STATEMENT We could improve the efficacy of brain stimulation to treat seizures by understanding the structure of synchrony. Electrical stimulation may disrupt seizures by desynchronizing neurons, but there is an uncertainty on which groups of neurons fire synchronously or chaotically during seizures. Here, we demonstrate that neurons linked by excitatory connections fire synchronously during seizures, and this synchrony is modulated by epileptogenesis and antiseizure drugs. Closed-loop brain stimulation carefully targeted to disrupt synchrony may improve the treatment of seizures.