Developmental emergence of transient and persistent hippocampal events and oscillations and their association with infant seizure susceptibility

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Abstract
During the second postnatal week in rats, the hippocampus exhibits a transient period of hyperexcitability. To systematically assess the relationship between the onset and end of this period and spontaneous hippocampal activity, we used silicon depth electrodes in unanaesthetized head-fixed rats from postnatal day (P)2 to P18. At all ages, hippocampal sharp waves (SPWs) were prominent in the EEG. Beginning at P6, however, marked changes in SPWs and associated oscillations were detected. SPW-related ‘gamma tails’ (60–100 Hz) and ‘ripples’ (140–200 Hz) were first observed at P6 and P7, respectively, and both oscillations persisted up to P18. Transiently, between P6 and P11, SPW duration decreased and the occurrence of SPW doublets increased. In addition, between P8 and P11, a subset of rats exhibited ‘spontaneous potentiated SPWs’ characterized by double polarity reversals, enhanced likelihood of gamma tails, and population spikes. Having identified a suite of transient hippocampal features consistent with a window of increased excitability, we next assessed whether electrographic seizure activity would be most easily induced during this period. To do this, kainic acid (KA; 200 ng/infusion) was infused into the hippocampus contralateral to the recording probe. KA did not induce seizure activity until P7 and reached peak effectiveness at P9. Thereafter, sensitivity to KA declined. All together, these findings provide in vivo neurophysiological support for the notion of a developmental window of heightened seizure susceptibility during the second postnatal week, and also suggest that spontaneous nonpathological hippocampal activity can be used to mark the onset and end of this period.