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Initiation of Spontaneous Epileptiform Events in the Rat Neocortex In Vivo

¹Department of Physiology and Biophysics, Georgetown University, Washington DC, 20057-1421; and ²Department of Physiology and Biophysics, College of Life Science, Peking University, Beijing, 100871, Peoples Republic of China

Submitted 2 March 2003; accepted in final form 3 October 2003

We used voltage-sensitive dye imaging to visualize the distribution of initiation sites of the spontaneous interictal-like spikes (sISs) in rat neocortex, in vivo, induced by bicuculline or picrotoxin over the exposed cortex. The initiation site was small (approximately 200 µm diam). On average each initiation site initiated 2.0 ± 0.8 sISs (9 animals, 499 sISs, 251 sites). This is significantly different from that in neocortical slices, where each initiation site initiated 30–100 sISs. The initiation sites were not randomly distributed. The distance between two consecutive sites tended to be either <800 or >1200 µm, suggesting a temporal "suppression annulus" surrounding each initiation site. Within the annulus, the likelihood for initiating the next sIS was reduced. Suppression annulus did not have a noticeable change in the presence of GABA_b antagonist, suggesting it did not depend on the GABA_b inhibition. We also applied bicuculline locally to a spot of 800 x 800 µm² for approximately 45 min. During this period approximately 1000 sISs occurred within the spot. Bicuculline or picrotoxin was then applied to the entire craniotomy window. The pretreatment created an obvious cluster of initiation sites. Around this cluster, the suppression annulus became obvious in individual animals. Our results suggest that, in disinhibited cortex, epileptiform events were initiated from small sites. The initiation sites may cluster in an area with increased local activity. Surrounding each initiation site there may be a temporal suppression annulus.

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