Slow endogenous activity transients and developmental expression of K+-Cl- cotransporter 2 in the immature human cortex

Spontaneous transients of correlated activity are a characteristic feature of immature brain structures, where they are thought to be crucial for the establishment of precise neuronal connectivity. Studies on experimental animals have shown that this kind of early activity in cortical structures is composed of long-lasting, intermittent network events, which undergo a developmental decline that is closely paralleled by the maturation of GABAergic inhibition. In order to examine whether similar events occur in the immature human cortex, we performed direct current-coupled electroencephalography (EEG) recordings from sleeping preterm babies. We show now that much of the preterm EEG activity is confined to spontaneous, slow activity transients. These transients are characterized by a large voltage deflection that nests prominent oscillatory activity in several frequency bands covering the whole frequency spectrum of the preterm EEG (< 0.1-30 Hz). The slow voltage deflections had an amplitude of up to 800 mu V. Most of these 'giant' events originated in the temporo-occipital areas, with a maximum rate of about 8/min, and their occurrence as well as amplitude showed a decline by the time of normal birth. In age-matched fetal brain tissue, this decrease in the spontaneous activity transients was associated with a developmental up-regulation of the neuronal chloride extruder K+-Cl- cotransporter 2, a crucial molecule for the generation of inhibitory GABAergic Cl- currents. Our work indicates that slow endogenous activity transients in the immature human neocortex are mostly confined to the prenatal stage and appear to be terminated in parallel with the maturation of functional GABAergic inhibition.