Abstracts

Rationale: Seizures have a predictable duration, implying that self-liming mechanisms activate during ictal events, but the key factors for seizure termination have not been fully clarified (Lado & Moshe, Epilepsia 2008, 49:1651-1664; Löscher & Köhling, Epilepsy Behav 2010, 19:105-13). Synchronization of activities in different cerebral areas towards the end of seizures has been observed and proposed as one of the mechanisms leading to seizure stop. Recently, increase in thalamo-cortical coupling has been reported during seizures recorded in patients with temporal lobe epilepsy (Guye et al., Brain 2006, 129:1917-1928; Evangelista et al., Front Neurol 2015, 6:192), suggesting a role of this condition in seizure end. Here we analyze seizure-like events (SLEs) recorded in reuniens nucleus of the thalamus (TH) and the coupling between TH and limbic region, namely hippocampus (HIPP) and medial entorhinal cortex (mEC), during different phases of SLEs. Methods: Electrophysiological experiments were performed in isolated guinea-pig brains maintained in vitro by arterial perfusion. SLEs were induced by 3-min administration of the GABAa receptor antagonist bicuculline methiodide (50µM) and field potentials were recorded in TH, HIPP and mEC. Visual inspection and cross-correlation (CC) analysis were executed to measure the coupling between pairs of recording sites during different phases of SLEs. Results: Eleven SLEs with low voltage fast activity (fa) at onset were analysed and revealed that TH activity features the same phases described for HIPP and mEC signals (Boido et al., Cereb Cortex. 2014; 24:163-73): preictal spikes, fa (at 20 Hz) at onset, irregular spiking, b-early (presenting short bursts with irregular frequency and variable duration) and b-late (with regular bursts showing a progressive decrease in frequency and increase in amplitude) phases. Analysis of the frequency content confirmed the similarity between TH and HIPP signals. Measurements of onset time delays (?t) between the first and the last activated structures during b-early and b-late bursts demonstrated a significant decrease in ?t (p=0.001) indicating a progressive synchronization of the activities in the final part of the SLEs. We also found that HIPP was the first activated structure in the majority of the b-early bursts, whereas during the b-late phase TH was the main leader of the activity. CC analysis between TH and HIPP revealed a significant increase of coupling in the last part of the SLE (b-early vs b-late bursts, pb-early vs b-late bursts, p < 0.05) with HIPP preceding mEC. For TH/mEC pair no trends were recognized in the interaction between the two structures.  Conclusions: Towards the end of the SLEs, epileptiform activities are more regular, synchronized and follows the TH-to-HIPP and HIPP-to-mEC routes. Our data suggest a role of TH in leading the activity at the end of the SLE. Funding: Italian Health Ministry (Progetto Finalizzato Giovani Ricercatori 2011-02348633).