Optogenetically induced seizure and the longitudinal hippocampal network dynamics.
Optogenetically induced seizure and the longitudinal hippocampal network dynamics.
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光遗传学诱导的癫痫发作和纵向海马网络动力学。
DOI：
10.1371/journal.pone.0060928
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mushiake H
中科院分区：
文献类型：
--
作者：
Osawa S;Iwasaki M;Hosaka R;Matsuzaka Y;Tomita H;Ishizuka T;Sugano E;Okumura E;Yawo H;Nakasato N;Tominaga T;Mushiake H
癫痫发作是一种以大量神经元异常超同步为特征的发作性自限性现象。然而，我们目前对癫痫发作动力学的了解仍然有限。在这里，我们提出了一种新的在体模型的海马样后放电，利用光遗传学，并报告调查的定向网络动态癫痫发作期间沿着隔颞（ST）轴的海马。重复脉冲光刺激应用于啮齿动物海马，其中通道视紫红质-2（ChR2）的表达，同时记录的局部场电位（LFPs）。在W-TChR2V4转基因（ChR2V-TG）大鼠和携带ChR2的腺相关病毒（AAV）载体转染的野生型大鼠中，在刺激后成功诱导癫痫样后放电。脉冲频率为10和20 Hz，占空比为0.05时，后放电诱导最佳。免疫组织化学c-Fos染色后，一个单一的诱导后放电证实整个海马神经元激活。将多触点阵列电极沿海马ST轴沿着插入，记录海马样后放电过程中的LFP。LFP的格兰杰因果关系分析显示信号流沿着ST方向双向但不对称增加。状态空间呈现的因果关系和一致性揭示了三个离散状态的神经元样后放电现象：1）静息状态; 2）后放电开始与中度的一致性和占主导地位的时间间隔到时间的因果关系;和3）后放电终止与增加的连贯性和占主导地位的时间间隔到间隔的因果关系。利用光遗传学技术建立了一种新的在体神经元样后放电模型，该模型具有可重复性和无伪影电生理观察的优点。我们的研究结果提供了额外的证据海马隔颞相互作用在体内癫痫发作动力学的潜在作用。在癫痫发作的发生和终止中，双向网络沿着ST海马分层工作。
Epileptic seizure is a paroxysmal and self-limited phenomenon characterized by abnormal hypersynchrony of a large population of neurons. However, our current understanding of seizure dynamics is still limited. Here we propose a novel in vivo model of seizure-like afterdischarges using optogenetics, and report on investigation of directional network dynamics during seizure along the septo-temporal (ST) axis of hippocampus. Repetitive pulse photostimulation was applied to the rodent hippocampus, in which channelrhodopsin-2 (ChR2) was expressed, under simultaneous recording of local field potentials (LFPs). Seizure-like afterdischarges were successfully induced after the stimulation in both W-TChR2V4 transgenic (ChR2V-TG) rats and in wild type rats transfected with adeno-associated virus (AAV) vectors carrying ChR2. Pulse frequency at 10 and 20 Hz, and a 0.05 duty ratio were optimal for afterdischarge induction. Immunohistochemical c-Fos staining after a single induced afterdischarge confirmed neuronal activation of the entire hippocampus. LFPs were recorded during seizure-like afterdischarges with a multi-contact array electrode inserted along the ST axis of hippocampus. Granger causality analysis of the LFPs showed a bidirectional but asymmetric increase in signal flow along the ST direction. State space presentation of the causality and coherence revealed three discrete states of the seizure-like afterdischarge phenomenon: 1) resting state; 2) afterdischarge initiation with moderate coherence and dominant septal-to-temporal causality; and 3) afterdischarge termination with increased coherence and dominant temporal-to-septal causality. A novel in vivo model of seizure-like afterdischarge was developed using optogenetics, which was advantageous in its reproducibility and artifact-free electrophysiological observations. Our results provide additional evidence for the potential role of hippocampal septo-temporal interactions in seizure dynamics in vivo. Bidirectional networks work hierarchically along the ST hippocampus in the genesis and termination of epileptic seizures.
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