Intermittency properties in a temporal lobe epilepsy model

Epilepsy Behav. 2023 Feb:139:109072. doi: 10.1016/j.yebeh.2022.109072. Epub 2023 Jan 16.

Abstract

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.

Keywords: Epilepsy biomarker; Epileptogenesis; Network; Optogenetics; Seizures; Synchronization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epilepsy*
  • Epilepsy, Temporal Lobe*
  • Humans
  • Neurons / metabolism
  • Seizures
  • Status Epilepticus* / metabolism