Samenvatting

Over time memories are believed to undergo a time-dependent reorganization in the brain through a process known as systems consolidation during which they become less dependent on the hippocampus and more dependent on the neocortical structures. This reorganization is accompanied by a generalization of the memory, meaning that it becomes less detailed and less accurate. However, emotionally arousing or highly stressful experiences seem to escape this pattern and be remembered stronger and longer even at remote time points. It has been shown that noradrenaline can alter the process of systems consolidation and maintain memories
accurate and episodic-like. Nevertheless, it remains unclear how it can alter this long-term trajectory of memory. Thus, in this research project, we aimed to investigate the effects of yohimbine, a noradrenergic stimulant, on the accuracy of memory at the level of the engram neurons within the hippocampus. For this, we used FosxTRAP2xROSA transgenic mice to permanently label neurons activated over a time window. We trained them on an object-in context task to form an episodic-like memory. The accuracy of the object-context association was tested at 3 days (for recent memory) and at 14 days (for remote memory). After testing and perfusing the mice, hippocampal slices were immunostained and imaged. The tdTomato and c-Fos-expressing cells (i.e., active during training and testing, respectively) and their overlap (i.e., reactivated cells) were counted. The latter were then correlated with the discrimination index of each mouse to assess memory performance. We found that yohimbine treated mice showed enhanced object-in-context memory accuracy 14 days after training while at recent memory recall, no differences were observed between the groups. We found no group differences in the percentage of c-Fos+ and tdTomato+ cells at both time points. The discrimination index and the reactivation rate during the remote memory testing of the 0.3 mg/kg yohimbine group were negatively correlated whilst in the recent memory recall we did not find a correlation in any of the groups. A crucial finding was that the reactivation rate of the hippocampal neurons in the vehicle group at recent memory recall was significantly higher compared to the reactivation at remote memory recall of the same group. This was not the case
for the 0.3 mg/kg yohimbine-treated group, indicating that yohimbine administration post training affects only remote memory recall since at a recent time point, memory is still dependent on the hippocampus and thus maintained accurate.