Changes in preferred firing phase have previously been descr
Changes in preferred firing phase have previously been described with regard to exposure to novelty (Douchamps et al., 2013) as well as between the center and side arms of a spatial alternation task (Schomburg et al., 2014). Our results show that phase modulation of cell activity, as well as robust phase shifts in response to cognitive demand, illustrate network purchase Mitiglinide Calcium or malfunction as a long-term consequence of pediatric seizures. Remarkably, the shifts in preferred phase preference between foraging and avoidance contexts, for both Cont and FSE-L brought the preferred firing phases of place cells in both CA1 and CA3 in register at a specific phase of theta. That CA3 phase preference was static in both groups and in both contexts suggests that the shift in phase preference in CA1 during active avoidance was not due to changes in spatial sampling. As this shift was not seen in FSE-NL, this implies that performance in the active avoidance task may not only be dependent on the temporal organization of action potentials within local theta but that this temporal organization must be aligned between CA1 and CA3 at the descending phase of local theta. Again, these results are very much in line with the notion that the recall of information requires the interaction of CA1 with stored information in CA3 (Hasselmo, 2005). Theta oscillations are strongly tied to processes in the hippocampus that integrate past and current position with projected position (Gupta et al., 2012; Itskov et al., 2008). The representation of space by theta-time-scale is similar for CA3-CA1 neuron pairs, yet the firing probabilities of CA1 and CA3 cells are different in the baseline foraging context. CA1 cells tend to fire toward the peak of local theta while CA3 cells are more active toward the trough. This anti-phase relationship is believed to be due to the functional connections within the CA3-CA1 circuit and the unique population dynamics of each region. Temporally coherent increases in gamma power in both regions occur while CA1 and CA3 pyramidal cell layer theta are at opposing levels of excitation (Buzsáki, 2006). This could explain the antithetical relationship we found between CA1 theta and CA3 slow gamma voltage correlations in Cont and FSE-L. In particular, the correlation between CA3 theta and CA1 slow gamma was even lower for FSE-L than Cont and may be related to the slower gamma frequency found in these animals. FSE-NL exhibited what may be considered a pathologically low cross-theta correlation between CA1 and CA3. Coupled with the observation that CA1 pyramidal cells exhibit temporal discoordination in CA1 with regard to hippocampal theta, our results suggest that a cause of FSE-NL difficulties with the active avoidance task is ineffective circuit coordination at CA1 synapses that are believed to actively regulate inputs from both CA3 at stratum radiatum and entorhinal cortex at straum lacunosum. The optimal interval between CA3 and entorhinal inputs for discharging CA1 pyramidal cells is 40–60ms, or half a theta cycle. The major implication here is that an active subset of CA3 cells can “predict” the animal\'s spatial location 40–60ms earlier. If the entorhinal input then “confirms” this prediction of spatial location, the CA1 pyramidal cells will become active. If not, the entorhinal input is insufficient to activate CA1 cells (Buzsáki, 2006). Therefore, to calculate current and projected position it is necessary for spike timing to be temporally accurate and for CA3 and CA1 to operate as a functional unit relative to entorhinal cortex inputs during theta. This functional connectivity between CA1 and CA3 is evident in the significant voltage correlations at theta frequency between CA1 and CA3 in animals that are able to learn the avoidance task. Because cross-theta correlations are low in FSE-NL, and CA1 cell activity is not temporally coordinated by theta in these animals, integration of CA1 action potentials with CA3 and entorhinal inputs would be impeded.