Mechanisms of memory formation and consolidation in hippocampal and cortical pyramidal mouse neurons

The roles of hippocampus and cortex in recent and remote memory processing is well assessed and the association of experience-dependent behavioural modifications with hippocampal and anterior cingulate cortical (ACC) neuron morphological changes at different time points after contextual fear conditioning has been characterised. Although the association between such morphological modifications and biochemical changes related deserves further characterisation. Here, we have previously observed that during the formation of recent contextual fear memory, hippocampal CA1 neurons display morphological changes in parallel with rapid accumulation of EphrinB2, a cell adhesion factor known, in association with its receptor(s), to influence synaptic plasticity and the dynamics of dendritic spines. To investigate whether this process may represent a general marker of induced neuronal plasticity, we studied the conversion of recent -to-remote memory, which ultimately depends on an increase in dendritic spine number of pyramidal neurons of the anterior cingulate cortex (ACC), by analysing the effect of contextual fear conditioning on EphrinB2 levels in these neurons. To this end, we determined dendritic complexity and EphrinB2 levels 24 hours (recent), 7 days (imtermediate) and 36 days (remote) after conditioning in C57BL/6N mice. We observed that EphrinB2 accumulation parallels the increase in spine density of CA1 neurons of conditioned mice, at the recent and intermediate time point, subsequently decreasing at the remote time point. In addition, a similar parallel pattern was observed for neuronal EphrinB2 levels and dendritic complexity in the ACC, which were both increased at the remote time point. The increase in EphrinB2 levels observed in the hipppocampus 24 hr post conditioning and in the ACC 36 days after was prevented by post-training anisomycin treatment. On the contrary, late anisomycin treatmen (24 days post conditioning) didn't prevent EphrinB2 increase in the cortex. These results suggest that accumulation of EphrinB2 is involved in memory-associated cellular modifications detected in both the hippocampus and ACC, and may therefore represent a more general biochemical marker of conditioning-induced neuronal rearrangements.