title: Interictal spikes in focal epileptogenesis.
abstract: Interictal electroencephalography (EEG) potentials in focal epilepsies are sustained by synchronous paroxysmal membrane depolarization generated by assemblies of hyperexcitable neurons. It is currently believed that interictal spiking sets a condition that preludes to the onset of an ictal discharge. Such an assumption is based on little experimental evidence. Human pre-surgical studies and recordings in chronic and acute models of focal epilepsy showed that: (i) interictal spikes (IS) and ictal discharges are generated by different populations of neuron through different cellular and network mechanisms; (ii) the cortical region that generates IS (irritative area) does not coincide with the ictal-onset area; (iii) IS frequency does not increase before a seizure and is enhanced just after an ictal event; (iv) spike suppression is found to herald ictal discharges; and (v) enhancement of interictal spiking suppresses ictal events. Several experimental evidences indicate that the highly synchronous cellular discharge associated with an IS is generated by a multitude of mechanisms involving synaptic and non-synaptic communication between neurons. The synchronized neuronal discharge associated with a single IS induces and is followed by a profound and prolonged refractory period sustained by inhibitory potentials and by activity-dependent changes in the ionic composition of the extracellular space. Post-spike depression may be responsible for pacing interictal spiking periodicity commonly observed in both animal models and human focal epilepsies. It is proposed that the strong after-inhibition produced by IS protects against the occurrence of ictal discharges by maintaining a low level of excitation in a general condition of hyperexcitability determined by the primary epileptogenic dysfunction.
authors.affiliation: Department of Experimental Neurophysiology, Istituto Nazionale Neurologico 'Carlo Besta', via Celoria 11, 20133, Milan, Italy. decurtis@istituto-besta.it
authors.forename: M
authors.initials: M
authors.lastname: de Curtis
authors.forename: G
authors.initials: G
authors.lastname: Avanzini
mesh_terms: D000200:Action Potentials; D015220:Calcium Channels / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009433:Neural Inhibition; D010507:Periodicity; D017470:Receptors, Glutamate / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D015220:Calcium Channels; D017470:Receptors, Glutamate; D015222:Sodium Channels