PATTERN AND PHARMACOLOGY OF PROPAGATING EPILEPTIFORM ACTIVITY IN MOUSE CEREBRAL-CORTEX

Multiple extracellular recording electrodes were used to study the int ra- and interhemispheric spread of stimulus-evoked epileptiform respon ses in adult mouse neocortical slices. Bath application of 20 mu M bic uculline methiodide induced epileptiform activity that propagated at s imilar to 0.08 m/s over several millimeters in rostro-caudal and medio -lateral direction within the ipsilateral hemisphere and across the co rpus callosum to the contralateral hemisphere. A vertical incision fro m layer II to subcortical regions did not prevent the spread to remote cortical regions, indicating that layer I plays a major role in the l ateral propagation of epileptiform activity. The intra- and interhemis pheric spread was not influenced by application of an N-methyl-D-aspar tate (NMDA) receptor antagonist, but blocked by an antagonist acting a t the lpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-t ype glutamate receptor. The potential role of potassium channel activa tion in controlling the generation or spread of epileptiform activity was tested by applying the potassium channel opener cromakalim and the serotonin type 1A (5-HT1A) receptor agonist (+/-)-8-hydroxydipropylam inotetralin (8-OH-DPAT) to the disinhibited slices. Whereas cromakalim reduced the neuronal excitability and blocked all epileptiform respon ses, 8-OH-DAPT did not affect the activity pattern. Our results sugges t that propagating epileptiform activity in disinhibited neocortical s tructures is predominantly mediated by activation of AMPA receptors an d controllable by activation of a voltage-dependent potassium current. (C) 1998 Academic Press.