Abstracts

Rationale: We wish to gain a better understanding of how the corpus callosum facilitates the propagation of epileptic seizures in the mammalian brain. Methods: 350 micron thick coronal slices from mouse anterior cingulate cortices were cut, preserving axonal connections across the corpus callosum. We produced epileptiform events via applicaton of bicuculline to both hemispheres simultaneously, as well as to single hemispheres. We measured neuronal activity electrophysiologically and optically, using extracellular electrodes and fluorescent calcium dye imaging, respectively. Results: Applying bicuculline evoked spontaneous epileptiform events. During simultaneous application to both hemispheres, these events can originate in one hemisphere and then evoke a similar event in the neighboring hemisphere, with latencies ranging from 15 to 300 msec. Usually the events originate consistently in a particular hemisphere, although there are counter-examples of the locus alternating from one hemisphere to the other. Preliminary results with bicuculline applied to a single hemisphere show the event originating in the applied hemisphere and then traveling to the other at longer latencies of several hundred msecs. We show that these coordinated events between hemispheres require the intact callosum, as the severing of this structure destroys any temporal correlation between these epileptiform events in the respective hemispheres, while preserving individual events in the isolated hemispheres. Further experiments are studying these phenomena using intracellular recordings in a range of seizure-provoking conditions. Conclusions: We have developed a viable in vitro cortical slice preparation for the study trans-callosal seizure propagation, allowing control of hemisphere-specific seizure conditions and the measurement of responses at multiple and single-cell levels.