Intermittency properties in a temporal lobe epilepsy model

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 sei-zures 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 con-tribute to abnormal epileptic seizure activity. In this work, we investigated how IAINs connectivity influ-ences 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 syn-chronous bursts and asynchronous spikes, respectively. Once the intermittent activity was properly char-acterized, 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.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

Neuronal synchronization is crucial for brain communication and learning, but changes in connectivity can lead to hyper-synchronized states associated with epileptic seizures. The ARC protein is linked to synaptic alterations and epilepsy. Intense ARC immunoreactive neurons (IAINs) with increased connectivity and conductance are observed during status epilepticus, potentially contributing to abnormal seizure activity. This study investigates how IAINs connectivity influences firing patterns and synchronization. Synchronized burst patterns and intermittent up and down activities are observed in neural networks with increased IAINs connectivity. Optogenetics control effectively suppresses synchronized bursts when IAINs are targeted, highlighting their important role in both generating and suppressing highly synchronous activities.