Sprouting fibers gain access to circuitry transsynaptically altered by kindling

In intact rats, “kindling” stimulation of the entorhinal cortex (EC) resulted, after an average of 23 daily stimulations, in the appearance of generalized convulsions. When the primary site of kindling in the EC was electrolytically destroyed and 14 days were permitted for the contralateral EC to sprout in response to the lesion, kindling stimulation of this surviving EC evoked fully developed motor seizures in 9 of 10 animals with the first or second stimulation. However, if the primary site of kindling was not destroyed, kindling via the contralateral EC required an average of more than five stimulations. Furthermore, if sprouting was induced by a unilateral EC lesion prior to any kindling stimulation, kindling via the surviving “sprouted” EC contralateral to the lesion proceeded at a rate not significantly different from normal. Finally, the essentially immediate expression of seizure-evoking capabilities via the EC contralateral to a lesion was not observed if kindling via the secondary site was initiated 1 day after a primary site lesion, at a time prior to the completion of sprouting. These results were consistent with the hypothesis that EC kindling results in transsynaptic alterations either in the immediate targets of the EC (e.g., the dentate gyrus) or further “downstream” synaptically, and that destruction of the primary site of kindling results in the sprouting of projections which gain access to the altered circuitry.