8 ± 0.05 Hz). Starting with P5 short episodes (0.2 ± 0.003 s, n = 1951 events from 19 pups) of low gamma-band (37.08 ± 0.15 Hz) oscillations overlaid spindle-shaped oscillations with main frequency of 9.2 ± 0.11 Hz and large amplitudes (251.61 ± 2.82 μV). Due to the tight connection between the superimposed gamma oscillations and the slow theta-alpha bursts, we defined this pattern of prefrontal activity as nested gamma spindle bursts (NG) (Figures 1B,

1Cii, and 1Ciii). They occurred at a frequency of 0.67 ± 0.09 bursts/min, lasted 2.12 ± 0.03 s and were accompanied (Figure 1Ciii) or not (Figure 1Cii) by MUA. Although the main difference between SB and NG was the presence of superimposed gamma episodes, the two patterns of prefrontal activity have also distinct properties (Figure S2). Similar to early urethane-independent oscillations in the primary sensory cortices prefrontal SB and NG were marginally modified by progressive reduction BIBW2992 mouse of the urethane dose from 1 to 0.125 g/kg body weight (n = 16 pups). Their occurrence and main frequency remained constant, whereas their amplitude decreased from 145 ± 7 μV to 107.7 ± 5.8 μV for Lumacaftor mouse SB and from 277.7 ± 10.1 μV to 160 ± 8 μV for NG. With ongoing maturation the properties of SB and NG modified significantly. Their occurrence, duration, amplitude, and dominant

frequency gradually increased with age (Figure 1E). Around P10–11 the PFC switched from discontinuous SB and NG to continuous oscillatory rhythms (Figures 1D and S4), suggesting that the neuronal networks generating oscillatory patterns underwent a substantial process of reorganization. The continuous rhythm with main frequency in theta-band (6.11 ± 0.03 Hz, n = 19 pups) and amplitudes ranging from 56 to 544 μV expressed

superimposed short episodes of gamma activity (Figure 1D). The amplitude and the dominant frequency of continuous oscillatory activity in the PFC were GBA3 relatively stable during the second postnatal week (Figure 1E). These results indicate that corresponding to the previously reported delayed anatomical maturation of the PFC, network activity emerges here later than in the V1 or S1 of age-matched rat pups. The presence of discontinuous and later of continuous theta-gamma rhythms mirrors early complex intra- and intercortical interactions. To gain a first insight into the network interactions leading to the generation of oscillatory patterns in the neonatal PFC we analyzed the relationship between neuronal discharge and SB/NG (Figure 2A). The mean firing rate during the whole recording was very low (0.67 ± 0.11 Hz, n = 7 pups), MUA predominantly accompanying the prefrontal oscillations. Only a low fraction of oscillation-associated spikes (15.7% ± 2.1%, n = 2479 spikes from 6 pups) was organized in bursts. When calculating separately the firing rate for SB and NG, a significantly (p < 0.001) higher spike discharge was associated with NG (14.