To estimate the causal strength of prefrontal-hippocampal interactions and its dynamics during development, Granger causality analysis, a powerful method for studying directed interactions between brain areas (Ding et al., 2000 and Anderson et al., 2010), was carried out for pairs of signals in theta-frequency band from the PFC and Hipp. Whereas the peak Granger causality values from the neonatal Cg to the CA1, denoted as Cg → Selleck MK 2206 Hipp (n = 5 pups), were not significantly different from those in the opposite direction, denoted as Hipp → Cg (Figure 5), a different causal relationship was found for the interaction between the neonatal PL and Hipp. The hippocampal theta bursts drove stronger

the prelimbic SB and NG than vice versa, since the peak Granger causality values were significantly higher for Hipp → PL than for the reciprocal connection PL → Hipp in all 10 investigated pups (Figure 5). The results are in line with the stable coupling between the PL and Hipp as revealed by coherence and cross-correlation analysis and support the driving role

of hippocampal theta bursts for the prelimbic oscillations. Toward the end of the second postnatal week the peak values of Granger causality for pairs of signals from the Cg or PL and Hipp were significant Selleck Decitabine in all investigated pups (n = 14), but similar for both directions (Figure 5). Thus, we suggest that with progressive maturation, prefrontal and hippocampal networks mutually influence each other. To identify the mechanisms underlying the directed communication between the developing PFC and Hipp, we assessed the spike-timing

relationships between prefrontal neurons and hippocampal theta bursts as well as between pairs of neurons from the two areas. Due to the very low firing rate of cingulate neurons and the results of Granger causality analysis, we focused the investigation on the prelimbic neurons. For this, we performed acute multitetrode recordings from the PL and Hipp of P7–8 (n = 7 pups) and P13–14 (n = 5 pups) rats. In a first instance, we tested whether prelimbic neurons are phase-locked to the hippocampal theta bursts. The analysis revealed that ∼9% of prelimbic neurons were Calpain significantly phase-locked to the hippocampal theta burst at both neonatal and prejuvenile age. In a second instance, we tested the impact of hippocampal firing on prelimbic cells and calculated the standardized cross-covariance (Qi,j) between all pairs (i, j) of simultaneously recorded prelimbic and hippocampal neurons (52 prelimbic neurons and 59 hippocampal neurons in P7–8 rats, 201 prelimbic neurons and 63 hippocampal neurons in P13–14 rats). In neonatal rats, only few neurons (287 PL-Hipp pairs from 3 pups) had a firing rate exceeding the set threshold of 0.05 Hz and were used for further analysis. The cross-covariance computed for all prelimbic-hippocampal pairs revealed no consistent spike timing of prelimbic neurons relative to the hippocampal cells, but yielded to a rather broad peak centered at ∼0 ms lag.