Mechanism of highly synchronized bilateral hippocampal activity.

Mechanism of highly synchronized bilateral hippocampal activity.
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DOI:
10.1016/j.expneurol.2013.11.014
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发表时间:
2014-01
影响因子:
5.3
通讯作者:
Durand, D. M.
Durand, D. M.
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Y.;Toprani, S.;Tang, Y.;Vrabec, T.;Durand, D. M.

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啮齿类动物大脑中癫痫样放电的体内研究表明,双侧癫痫发作活动有时可以以非常小的延迟(< 2 ms)同步。考虑到跨半球的生理传播时间(> 6 ms),观察到的左右CA 3区域之间的癫痫样活动的小时间延迟是出乎意料的。本研究的目的是通过体外电生理技术和计算机模拟来确定这种紧密同步的机制。共同来源的假设首先通过使用含有具有功能性腹侧海马连合(VHC)的海马和无其他组织的体外制剂来消除。接下来,通过低噪音体内记录和噪音环境的计算机模拟,排除了噪音基线可能掩盖两个半球之间潜在同步活动的假设。然后,我们建立了一个新的双边CA 3模型来测试的假设,非常小的左向右传播延迟的癫痫活动的现象是癫痫细胞网络动力学的产物。我们发现,连合道连接可以减少从两侧记录的癫痫发作事件之间的延迟,而活动则沿着CA 3层纵向传播,从而产生比两侧之间的传播时间小得多的延迟。建模结果表明,需要经常性和前馈抑制缩短双边传播延迟,并严重依赖于连合纤维束的长度以及参与癫痫发作的细胞数量。这些结合的建模/实验研究表明,考虑到海马网络的结构,有可能解释两个半球之间近乎完美的同步。
In vivo studies of epileptiform discharges in the hippocampi of rodents have shown that bilateral seizure activity can sometimes be synchronized with very small delays (< 2 ms). This observed small time delay of epileptiform activity between the left and right CA3 regions is unexpected given the physiological propagation time across the hemispheres (> 6 ms). The goal of this study is to determine the mechanisms of this tight synchronization with in-vitro electrophysiology techniques and computer simulations. The hypothesis of a common source was first eliminated by using an in-vitro preparation containing both hippocampi with a functional ventral hippocampal commissure (VHC) and no other tissue. Next, the hypothesis that a noisy baseline could mask the underlying synchronous activity between the two hemispheres was ruled out by low noise in-vivo recordings and computer simulation of the noisy environment. Then we built a novel bilateral CA3 model to test the hypothesis that the phenomenon of very small left-to-right propagation delay of seizure activity is a product of epileptic cell network dynamics. We found that the commissural tract connectivity could decrease the delay between seizure events recorded from two sides while the activity propagated longitudinally along the CA3 layer thereby yielding delays much smaller than the propagation time between the two sides. The modeling results indicate that both recurrent and feedforward inhibition were required for shortening the bilateral propagation delay and depended critically on the length of the commissural fiber tract as well as the number of cells involved in seizure generation. These combined modeling/experimental studies indicate that it is possible to explain near perfect synchronization between the two hemispheres by taking into account the structure of the hippocampal network.
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