Speaker
Description
Neuronal synchronisation is essential for effective brain communication, but abnormal connectivity changes can lead to hypersynchronized states associated with epileptic seizures. In this regard, the activity-regulated cytoskeleton-associated protein (ARC) has been implicated in synaptic alterations related to epilepsy. For this reason, we investigated how ARC-immunoreactive neurons (IAINs) can influence neuronal network dynamics, particularly firing patterns and synchronisation levels, aiming to understand their role in both the generation and suppression of activities associated with epilepsy. The research used immunofluorescence analysis of ARC in hippocampal sections to characterise IAINs following the induction of status epilepticus in rodents. Based on this, a neuronal network model consisting of adaptive exponential integrate-and-fire neurons (AdEx) was developed to investigate the influence of such IAINs on the emergence of intermittent activities. The model simulated intermittent behaviours, considering the impact of IAIN connectivity through increases in the strength and number of connections. Increasing the fraction and synaptic conductance of excitatory IAINs resulted in synchronised burst firing within the network. Furthermore, these alterations favoured the emergence of intermittent firing patterns, characterised by transitions between synchronous bursts and asynchronous spikes, reminiscent of the up and down states of neural activity. As the strength of IAIN connections increased, hypersynchronized burst events became more prevalent, with durations extending beyond tens of minutes. Power-law and exponential distributions were used to fit the temporal characteristics of these events, which can be associated, for example, with mild-to-moderate and severe epilepsy. In this context, the optogenetic control of highly synchronous bursts was effective when targeting IAINs but not non-IAINs. The proposed model provides insights into the mechanisms underlying epileptic network dynamics and offers a foundation for future studies aiming to develop novel interventions for epilepsy management.
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