5 ± 0.42 Hz, n = 7 pups) and was mainly confined to their gamma episodes (42.29 ± 1.83 Hz) (Figure 2B). However, the majority (77% ± 17%) of nested gamma episodes were not associated with MUA discharge (Figure 1Cii versus 1Ciii). When occurring together, gamma episodes and MUA were tightly coupled and a prominent peak in their cross-correlogram emerged 30 to 50 ms after the onset of gamma episodes (Figure 2C). The prominent increase in the firing rate during

gamma episodes was preceded by an ∼50 ms long period of low MUA, during which the occurrence probability of gamma episodes was also very low. Examination of spike-gamma phase relationship showed that 12 out of 13 prefrontal Palbociclib manufacturer neurons (n = 10 pups) fired shortly after the trough of gamma cycle (Figure 2D). This gamma phase-locking of prefrontal neurons suggests that the gamma episodes time the firing of the neonatal PFC. Antidiabetic Compound Library cell assay Moreover, the entrainment of local networks in gamma rhythms occurred not randomly, but timed by the underlying slow

rhythm of NG (NG cycle). The gamma episodes occur with the highest probability shortly before the trough of the NG cycle (Figure 2E). These results indicate that complex mechanisms control the neuronal firing in the neonatal PFC. The prefrontal neurons fire phase-locked to the nested gamma episodes that are, in turn, clocked by the underlying slow rhythm of NG. According to their location and cytoarchitecture several subareas can be functionally distinguished within the PFC as early as P6 (Van Eden and Uylings, 1985). Multielectrode recordings were performed simultaneously in the dorsally located anterior cingulate cortex

(Cg) as well as in the subjacent prelimbic cortex (PL) to characterize the spatial organization of the network activity over the developing PFC. Although SB and NG were present in both regions, their occurrence however significantly differed between the Cg and PL (Figure 3A; Table S2). In the Cg, SB represented the dominant pattern of activity, very few NG being present in this area. In contrast, NG are the dominant pattern of prelimbic activity. Moreover, the duration, main frequency, power, and frequency distribution of SB as well as the amplitude and power of NG showed significant differences in the Cg and PL (Table S2). Beside different properties, SB and NG showed also distinct current generators over the Cg and PL as indicated by the current source density (CSD) analysis performed on 38 SB and 69 NG from 5 pups (Figure 3B). The most common CSD profile for SB present in 43.05% ± 11.7% of events was a narrow source-sink pair confined to the upper cingulate area. In contrast, the majority of NG (72.03% ± 7.34%) showed a prominent sink within the PL. In the majority of recordings, neither SB nor NG were restricted to one channel but rather occurred simultaneously at several neighboring recording sites of the 4×4 array electrode (Figures 3C and 3D).