InvolvementofUbiquitin-Proteasome System Dependent Protein Degradation In Memory Performance

Memory is the basis of cognitive abilities and plays a vital role in daily life. Memory consolidation is a dynamic process which relies on use-dependent protein turnover. Protein degradation as an important aspect of protein turnover is believed to be involved in memory consolidation. The mechanism underlying memory consolidation is widely studied; however, the processes of memory decline in response to new memory tasks remains open. My study aims to investigate the interaction of the proteasome and new memory tasks (novelty) on passive avoidance fear memory consolidation and retrieval.I studied the role of proteasome dependent protein degradation in memory consolidation and retrieval in mice using a one-trial passive avoidance paradigm and subcutaneous administration of the proteasome inhibitor MG132. In addition, I analyzed the efficiency of MG132 administration on proteasome activity in brain using a 20S proteasome activity assay kit. I observed an inhibition of hippocampal proteasome activity with 0.5-1.5 hours after injection which recovered to baseline level in 7-24 hours.Regarding effects on memory processing, I found that subcutaneously injected MG132 3 hours before training and 1.5 hours before test sessions caused a significant inhibition of memory acquisition and retrieval. Further I studied protein degradation mediated memory decline in response to new memory tasks, such as open field exploration (OF, novelty) and place object recognition task. At a proteasome inhibitor concentration that did not produce a significant effect on memory retrieval, a significant effect was only detected when novelty tasks were applied 1 hour before memory retrieval (test).In summary, I show that proteasome dependent protein degradation is involved in memory acquisition and in memory retrieval. In addition, novelty at different time points after passive avoidance learning has different effects on memory retrieval. Thus I conclude that inhibition of proteasome dependent protein degradation enhances the effects of novelty on already established memories.