Department of Physiology and Pharmacology, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA; Center for Mathematics, Computation, and Cognition, Federal University of ABC, São Bernardo do Campo, SP, Brazil.
Graduate in Science Program - Physics, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
Epilepsy Behav. 2023 Feb;139:109072. doi: 10.1016/j.yebeh.2022.109072. Epub 2023 Jan 16.
Neuronal synchronization is important for communication between brain regions and plays a key role in learning. However, changes in connectivity can lead to hyper-synchronized states related to epileptic seizures that occur intermittently with asynchronous states. The activity-regulated cytoskeleton-associated protein (ARC) is related to synaptic alterations which can lead to epilepsy. Induction of status epilepticus in rodent models causes the appearance of intense ARC immunoreactive neurons (IAINs), which present a higher number of connections and conductance intensity than non-IAINs. This alteration might contribute to abnormal epileptic seizure activity. In this work, we investigated how IAINs connectivity influences the firing pattern and synchronization in neural networks. Firstly, we showed the appearance of synchronized burst patterns due to the emergence of IAINs. Second, we described how the increase of IAINs connectivity favors the appearance of intermittent up and down activities associated with synchronous bursts and asynchronous spikes, respectively. Once the intermittent activity was properly characterized, we applied the optogenetics control of the high synchronous activities in the intermittent regime. To do this, we considered that 1% of neurons were transfected and became photosensitive. We observed that optogenetics methods to control synchronized burst patterns are effective when IAINs are chosen as photosensitive, but not effective in non-IAINs. Therefore, our analyses suggest that IAINs play a pivotal role in both the generation and suppression of highly synchronized activities.
神经元同步对于脑区之间的通讯非常重要,并且在学习中起着关键作用。然而,连接的变化会导致与间歇性的非同步状态相关的超同步状态。活性调节细胞骨架相关蛋白(ARC)与突触改变有关,而突触改变可能导致癫痫。在啮齿动物模型中诱导癫痫持续状态会导致强烈的 ARC 免疫反应性神经元(IAINs)的出现,IAINs 比非 IAINs 具有更多的连接和电导强度。这种改变可能导致异常的癫痫发作活动。在这项工作中,我们研究了 IAINs 的连接如何影响神经网络的发放模式和同步。首先,我们表明由于 IAINs 的出现出现了同步爆发模式。其次,我们描述了 IAINs 连接的增加如何有利于间歇性的上下活动的出现,分别与同步爆发和异步尖峰相关。一旦间歇性活动得到适当的描述,我们就应用光遗传学控制间歇性节律中的高同步活动。为此,我们考虑到 1%的神经元被转染并变得对光敏感。我们观察到,当选择 IAINs 作为光敏时,光遗传学方法控制同步爆发模式是有效的,但在非 IAINs 中则无效。因此,我们的分析表明,IAINs 在高度同步活动的产生和抑制中起着关键作用。