Mechanisms of Epileptiform Synchronization in Cortical Neuronal Networks
Affiliation: Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, PQ, Canada, H3A 2B4.
Keywords: Entorhinal cortex, extracellular Ca2+ concentration, extracellular K+ concentration, GABA, high frequency oscillations,
hippocampus, ictal discharges, interictal spikes, seizure onset, temporal lobe epilepsy.
Neuronal synchronization supports different physiological states such as cognitive functions and sleep, and it is
mirrored by identifiable EEG patterns ranging from gamma to delta oscillations. However, excessive neuronal synchronization
is often the hallmark of epileptic activity in both generalized and partial epileptic disorders. Here, I will review the
synchronizing mechanisms involved in generating epileptiform activity in the limbic system, which is closely involved in
the pathophysiogenesis of temporal lobe epilepsy (TLE). TLE is often associated to a typical pattern of brain damage
known as mesial temporal sclerosis, and it is one of the most refractory adult form of partial epilepsy. This epileptic disorder
can be reproduced in animals by topical or systemic injection of pilocarpine or kainic acid, or by repetitive electrical
stimulation; these procedures induce an initial status epilepticus and cause 1-4 weeks later a chronic condition of recurrent
limbic seizures. Remarkably, a similar, seizure-free, latent period can be identified in TLE patients who suffered an initial
insult in childhood and develop partial seizures in adolescence or early adulthood. Specifically, I will focus here on the
neuronal mechanisms underlying three abnormal types of neuronal synchronization seen in both TLE patients and animal
models mimicking this disorder: (i) interictal spikes; (ii) high frequency oscillations (80-500 Hz); and (iii) ictal (i.e., seizure)
discharges. In addition, I will discuss the relationship between interictal spikes and ictal activity as well as recent
evidence suggesting that specific seizure onsets in the pilocarpine model of TLE are characterized by distinctive patterns
of spiking (also termed preictal) and high frequency oscillations.
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