PT  - JOURNAL ARTICLE
AU  - Kile P. Mangan
AU  - Aaron B. Nelson
AU  - Steven Petrou
AU  - Chiara Cirelli
AU  - Mathew V. Jones
TI  - Cortical Tonic Inhibition Regulates the Expression of Spike-and-Wave Discharges Associated with Absence Epilepsy
AID  - 10.1101/164947
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 164947
4099  - http://biorxiv.org/content/early/2017/07/17/164947.short
4100  - http://biorxiv.org/content/early/2017/07/17/164947.full
AB  - Synchronous and bilateral spike-and-wave discharges accompany nonconvulsive behavioral and cognitive arrest during seizures associated with absence epilepsy. Previous investigation of multiple absence animal models suggests that the underlying cause of absence seizures is an increase in thalamic inhibitory tonic currents. In contrast, in this study we provide evidence that the level of cortical tonic inhibition also regulates absence seizure expression. Using continuous video-EEG recordings to monitor absence seizures and spike-and-wave discharge expression we show that pharmacological blockade of cortical tonic inhibition provokes absence seizures in wild-type mice. Furthermore, we show that pharmacological rescue of cortical tonic inhibition in an absence mouse (γ2R43Q) model, which lacks tonic inhibition, suppresses absence seizure and spike-and-wave discharge expression. Collectively, these results suggest an optimum level of tonic inhibition in the thalamocortical circuit is required for normal functioning and that a deviation from this optimum results in aberrant thalamocortical function, SWDs and absence seizures.