Excitation-Inhibition Balance in Absence Seizure Ictogenesis

Abstract Thirty percent of children with absence seizures are pharmaco-resistant, and 60% suffer from neuropsychiatric comorbidities that often persist even after full pharmacological control of the seizures. This highlights the need for a detailed comprehension of the cellular and network mechanisms of these nonconvulsive seizures. Generally, network hyperexcitability and hypersynchrony underlying seizure ictogenesis are thought to originate from impaired inhibition or enhanced excitation. In absence seizures, there is a markedly enhanced synchrony in cortico-thalamic and cortico-basal ganglia-thalamic networks, but solid evidence from genetic animal models indicates that at the single-cell and neuronal population levels GABAergic inhibition is generally increased while excitation is mostly either unchanged or decreased. Here, recent results on intrinsic conductances and network mechanisms within cortico-thalamic and cortico-basal ganglia-thalamic circuits are highlighted that support this view.