Pattern and pharmacology of propagating epileptiform activity in mouse cerebral cortex.
Multiple extracellular recording electrodes were used to study the intra- and interhemispheric spread of stimulus-evoked epileptiform responses in adult mouse neocortical slices. Bath application of 20 microM bicuculline methiodide induced epileptiform activity that propagated at approximately 0.08 m/s over several millimeters in rostro-caudal and medio-lateral direction within the ipsilateral hemisphere and across the corpus callosum to the contralateral hemisphere. A vertical incision from layer II to subcortical regions did not prevent the spread to remote cortical regions, indicating that layer I plays a major role in the lateral propagation of epileptiform activity. The intra- and interhemispheric spread was not influenced by application of an N-methyl-d-aspartate (NMDA) receptor antagonist, but blocked by an antagonist acting at the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor. The potential role of potassium channel activation 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-hydroxydipropylaminotetralin (8-OH-DPAT) to the disinhibited slices. Whereas cromakalim reduced the neuronal excitability and blocked all epileptiform responses, 8-OH-DAPT did not affect the activity pattern. Our results suggest that propagating epileptiform activity in disinhibited neocortical structures is predominantly mediated by activation of AMPA receptors and controllable by activation of a voltage-dependent potassium current.
Alefeld
M
M
Institute of Neurophysiology, University of Düsseldorf, Düsseldorf, D-40001, Germany.
Sutor
B
B
Luhmann
H J
HJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology*; D003337:Corpus Callosum / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D066298:In Vitro Techniques; D051379:Mice; D008839:Microelectrodes; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000494:pharmacology
D000927:Anticonvulsants; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D012702:Serotonin Antagonists