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1 Physiology and Biophysics, Peking University, Beijing, China; Physiology and Biophysics, Georgetown University, Washington, DC, USA
2 Physiology and Biophysics, Peking University, Beijing, China
3 Physiology and Biophysics, Georgetown University, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: wuj{at}georgetown.edu.
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 (~200 µm in diameter). On average each initiation site initiated 2.0±0.8 sISs (nine 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 ~45 minutes. During this period ~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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