Connectivity and Neuronal Synchrony during Seizures

Abstract

There is uncertainty regarding when and which groups of neurons fire synchronously during seizures. While several studies found heterogeneous firing during seizures, others suggested synchronous neuronal firing in the seizure core. We tested whether neuronal activity during seizures is orderly in the direction of the excitatory neuronal connections in the circuit. There are strong excitatory connections laterally within the septotemporally organized lamella and inhibitory trans-lamellar connections in the hippocampus, which allow testing of the connectivity hypothesis. We further tested whether epileptogenesis enhances synchrony and antiseizure drug administration disrupts it. We recorded local field potentials from CA1 pyramidal neurons using a small microelectrode array and kindled rats by a rapid, recurrent hippocampal stimulation protocol. We compared cross-correlation, theta phase synchronization, entropy, and event synchronization. These analyses revealed that the firing pattern was correlated along the lamellar, but not the septotemporal, axis during evoked seizures. During kindling, neuronal synchrony increased along the lamellar axis, while synchrony along the septotemporal axis remained relatively low. Additionally, the theta phase distribution demonstrated that CA1 pyramidal cell firing became preferential for theta oscillation negative peak as kindling progressed in the lamellar direction but not in the trans-lamellar direction. Last, event synchronization demonstrated that neuronal firings along the lamellar axis were more synchronized than those along the septotemporal axis. There was a marked decrease in synchronization and phase preference after treatment with phenytoin and levetiracetam. The synchrony structure of CA1 pyramidal neurons during seizures and epileptogenesis depends on anatomic connectivity and plasticity.

Ictal neural oscillatory alterations precede sudden unexpected death in epilepsy

“…Abnormal connectivity of brain networks plays a fundamental role in epilepsy. 40 , 41 We next examined the synchronization between M1 of cortex and DR of brainstem and explored frequencies at which synchrony occurs during the baseline and ictal states of fatal and non-fatal seizures. We found similar connectivity of M1 and DR during baseline recordings between survivors and non-survivors ( Supplemental Fig.…”

Extrahippocampal Seizure and Memory Circuits Overlap

“…The inhibitory tone might also play a role in shaping the seizure circuit. During kindling, neuronal firing and synchrony are more correlated along the lamellar hippocampal axis that contains excitatory connections than along the septotemporal axis that has inhibitory connections ( Ren et al, 2021 ). Propagation of seizures through the hippocampus is gated by strong inhibition of the DG ( Krook-Magnuson et al, 2015 ).…”

Early impairments of visually-driven neuronal ensemble dynamics in the rTg4510 tauopathy mouse model

“…Thus, we propose that a more pronounced pathological hyper-synchronized network might result in higher susceptibility to epileptogenesis in rTg4510 mice. As hyper-synchronicity was displayed in epileptiform activity loci during seizures in patients and rats [79, 80] and tauopathy mouse models displayed higher susceptibility to epileptogenesis [35, 45], these findings point to a potential translatable mechanism underlying subclinical epilepsy that was often reported in AD patients [31, 32]. Building on the aforementioned studies, our data also suggest that tau pathology increases network vulnerability to epileptiform activity in absence of amyloid-β pathology, which is typically implicated in this pathophysiology [29, 81].…”