Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy

Low-voltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTLE in vivo and in vitro, and these studies have highlighted the predominant involvement of distinct neuronal network/neu-rotransmitter receptor signaling in each of them. First, LVF onset seizures in epileptic rodents can originate from several limbic structures, frequently spread, and are associated with high frequency oscillations (HFOs) in the ripple band (80-200 Hz), while HYP onset seizures initiate in the hippocampus, and tend to remain focal with predominant fast ripples (250-500 Hz). Second, in vitro intracellular recordings from principal cells in limbic areas indicate that pharmacologically induced, seizure-like discharges with LVF onset are initiated by a synchronous inhibitory event or by a hyperpolarizing IPSPs barrage; in contrast, HYP onset is associated with a progressive impairement of inhibition and concomitant unrestrained enhance¬ment of excitation. Finally, in vitro optogenetic experiments show that under comparable experimental conditions (i.e., 4-aminopyridine application), the initiation of LVF or HYP onset seizures depends on the preponderant involvement of interneuronal or principal cell networks, respec¬tively. Overall, these data may provide insight to delineate better therapeutic targets in the treatment of patients presenting with MTLE and, perhaps, with other epileptic disorders as well.

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