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Current Neuropharmacology


ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Evolving Mechanistic Concepts of Epileptiform Synchronization and their Relevance in Curing Focal Epileptic Disorders

Author(s): Maxime Lévesque, David Ragsdale and Massimo Avoli*

Volume 17, Issue 9, 2019

Page: [830 - 842] Pages: 13

DOI: 10.2174/1570159X17666181127124803


The synchronized activity of neuronal networks under physiological conditions is mirrored by specific oscillatory patterns of the EEG that are associated with different behavioral states and cognitive functions. Excessive synchronization can, however, lead to focal epileptiform activity characterized by interictal and ictal discharges in epileptic patients and animal models. This review focusses on studies that have addressed epileptiform synchronization in temporal lobe regions by employing in vitro and in vivo recording techniques. First, we consider the role of ionotropic and metabotropic excitatory glutamatergic transmission in seizure generation as well as the paradoxical role of GABAA signaling in initiating and perhaps maintaining focal seizure activity. Second, we address non-synaptic mechanisms (which include voltage-gated ionic currents and gap junctions) in the generation of epileptiform synchronization. For each mechanism, we discuss the actions of antiepileptic drugs that are presumably modulating excitatory or inhibitory signaling and voltage-gated currents to prevent seizures in epileptic patients. These findings provide insights into the mechanisms of seizure initiation and maintenance, thus leading to the development of specific pharmacological treatments for focal epileptic disorders.

Keywords: Epileptiform synchronization, mesial temporal lobe epilepsy, interictal spikes, seizures, anti-epileptic drugs, excitatory transmission, inhibitory transmission, voltage-gated channels.

Graphical Abstract
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