title: Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy.
abstract: In different animal models of focal epilepsy, seizure-like ictal discharge propagation is transiently opposed by feedforward inhibition. The specific cellular source of this signal and the mechanism by which inhibition ultimately becomes ineffective are, however, undefined. We used a brain slice model to study how focal ictal discharges that were repetitively evoked from the same site, and at precise times, propagate across the cortex. We used Ca(2+) imaging and simultaneous single/dual cell recordings from pyramidal neurons (PyNs) and different classes of interneurons in rodents, including G42 and GIN transgenic mice expressing the green fluorescence protein in parvalbumin (Pv)-fast spiking (FS) and somatostatin (Som) interneurons, respectively. We found that these two classes of interneurons fired intensively shortly after ictal discharge generation at the focus. The inhibitory barrages that were recorded in PyNs occurred in coincidence with Pv-FS, but not with Som interneuron burst discharges. Furthermore, the strength of inhibitory barrages increased or decreased in parallel with increased or decreased firing in Pv-FS interneurons but not in Som interneurons. A firing impairment of Pv-FS interneurons caused by a membrane depolarization was found to precede ictal discharge onset in neighbouring pyramidal neurons. This event may account for the collapse of local inhibition that allows spatially defined clusters of PyNs to be recruited into propagating ictal discharges. Our study demonstrates that Pv-FS interneurons are a major source of the inhibitory barrages that oppose ictal discharge propagation and raises the possibility that targeting Pv-FS interneurons represents a new therapeutic strategy to prevent the generalization of human focal seizures.
authors.affiliation: Institute of Neuroscience, National Research Council and Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cammarota
authors.forename: Gabriele
authors.initials: G
authors.lastname: Losi
authors.forename: Angela
authors.initials: A
authors.lastname: Chiavegato
authors.forename: Micaela
authors.initials: M
authors.lastname: Zonta
authors.forename: Giorgio
authors.initials: G
authors.lastname: Carmignoto
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000503:physiopathology*; D004195:Disease Models, Animal; D004828:Epilepsies, Partial / Q000503:physiopathology*; D059330:GABAergic Neurons / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000503:physiopathology*
chemical_list: D002118:Calcium