Maturation of kainate-induced epileptiform activities in interconnected intact neonatal limbic structures in vitro

In vivo studies suggest that ontogenesis of limbic seizures is determined b y the development of the limbic circuit. We have now used the newly-develop ed in vitro intact interconnected neonatal rat limbic structures preparatio n to determine the developmental profile of kainate-induced epileptiform ac tivity in the hippocampus and its propagation to other limbic structures. W e report gradual alterations in the effects of kainate during the first pos tnatal week on an almost daily basis; from no epileptiform activity at birt h, through interictal seizures around postnatal day (P) 2 and ictal seizure s by the end of the first week. The developmental profile of kainate-induce d hippocampal seizures is paralleled by the expression of postsynaptic kain ate receptor-mediated currents in CA3 pyramidal cells. Intralimbic propagat ion of the hippocampal seizures is also age-dependent: whereas seizures rea dily propagate to the septum and to the contralateral hippocampus via the c ommissures on P2, propagation to the entorhinal cortex only takes place fro m P4 onwards. Finally, repeated brief applications of kainate to the hippoc ampus induce recurrent spontaneous glutamatergic ictal and interictal disch arges which persist for several hours after the kainate is washed away and which replace the physiological pattern of network activity. Paroxysmal act ivities are thus generated by kainate in the hippocampus at an early develo pmental stage and are initially restricted to this structure. Before the en d of the first week of postnatal life, kainate generates the epileptiform a ctivities that may perturb activity-dependent mechanisms that modulate neur onal development. Although at this stage neurons are relatively resistant t o the pathological effects of kainate, the epileptiform activities that it generates will perturb activity-dependent mechanisms that modulate neuronal development.