Abstract
Brain function depends on a balance between excitation and inhibition. Feed-forward inhibition (FFI) within the brain controls the firing of principal excitatory neurons and prevents runaway excitation. It is primarily mediated by parvalbumin-expressing (PV+) inhibitory interneurons. Abnormal functioning of these interneurons leads to neurological disorders, including epileptic seizures. In the cortico-thalamocortical (CTC) network, dysfunctional FFI has been implicated in absence seizure generation. The hallmark of absence seizures is spike-wave discharges (SWDs) measuring 3-4 Hz on an electroencephalogram (EEG) with concomitant behavioural arrests termed absences.
Our laboratory has previously reported defects in the activation of PV+ interneurons in the stargazer mouse model of absence epilepsy, which could underlie hypersynchronous excitation leading to seizures. The aim of the current study was to investigate the impact of dysfunctional FFI within CTC network on absence seizure generation and behaviour.