Evolution of Network Synchronization during Early Epileptogenesis Parallels Synaptic Circuit Alterations

Abstract

In secondary epilepsy, a seizure-prone neural network evolves during the latent period between brain injury and the onset of spontaneous seizures. The nature of the evolution is largely unknown, and even its completeness at the onset of seizures has recently been challenged by measures of gradually decreasing intervals between subsequent seizures. Sequential calcium imaging of neuronal activity, in the pyramidal cell layer of mouse hippocampal in vitro preparations, during early post-traumatic epileptogenesis demonstrated rapid increases in the fraction of neurons that participate in interictal activity. This was followed by more gradual increases in the rate at which individual neurons join each developing seizure, the pairwise correlation of neuronal activities as a function of the distance separating the pair, and network-wide measures of functional connectivity. These data support the continued evolution of synaptic connectivity in epileptic networks beyond the latent period: early seizures occur when recurrent excitatory pathways are largely polysynaptic, while ongoing synaptic remodeling after the onset of epilepsy enhances intranetwork connectivity as well as the onset and spread of seizure activity.

Perfused drop microfluidic device for brain slice culture-based drug discovery

“…5d, n = 5). These activity patterns and epilepsy progression were similar to previous observations in organotypic hippocampal cultures maintained with traditional methods (Dyhrfjeld-Johnsen, Berdichevsky et al 2010, Berdichevsky, Dzhala et al 2012, Berdichevsky, Dryer et al 2013, Lillis, Wang et al 2015).…”

Organization and control of epileptic circuits in temporal lobe epilepsy

“…Once details of epileptic circuits are known at small and large scales, controlling the circuit may become possible. There are a wide variety of techniques other than anatomy or electrophysiology which may be useful for continuing to helping to map out these circuits including an innovative type of high-resolution microscopy called STORM (Dani et al, 2010; Dudok et al, 2015), calcium imaging (Feldt Muldoon et al, 2013; Lillis et al, 2015), voltage-sensitive dyes (Takano and Coulter, 2012), multielectrode arrays, and optogenetic techniques (Bui et al, 2015). Other techniques which may allow control of pathologically hyperexcitable networks either in animal models or patients include cell transplant (Henderson et al, 2014), designer receptors exclusively activated by designer drugs, aka DREADDs (reviewed in Krook-Magnuson and Soltesz, 2015), responsive neurostimulation, and deep brain stimulation (Bui et al, 2015).…”

Reliable and Elastic Propagation of Cortical Seizures In Vivo

“…Electrical recordings are inherently sparse when compared to the actual neural population density, complicating definitive conclusions. On the other hand, the few in vitro reports employing high-resolution optical imaging of ictal networks had too low temporal resolution to uncover the true spatiotemporal dynamics of ictal networks (Badea et al, 2001; Cammarota et al, 2013; Feldt Muldoon et al, 2013; Lillis et al, 2015; Neubauer et al, 2014; Tashiro et al, 2002; Trevelyan et al, 2007). To this date, there have been only two studies using optical methods to measure the recruitment of epileptic networks at cellular scale in vivo (Baird-Daniel et al, 2017; Muldoon et al, 2015).…”