Mechanisms of memory labilization

FUSTIÑANA, MARIA SOL; DE LA FUENTE, VERÓNICA; FEDERMAN, NOEL; FREUDENTHAL, RAMIRO; ROMANO, ARTURO

Munich

Congreso; European Brain and Behaviour Society Meeting; 2013

European Brain and Behaviour Society

The ubiquitin-proteasome system (UPS) of protein degradation has been evaluated in different forms of neural plasticity and memory, both in vertebrates and invertebrates. The role of UPS in such processes is controversial. Several results support the idea that the activation of this system in memory consolidation is necessary to overcome negative constrains for plasticity. In this case, the inhibition of the UPS during consolidation impairs memory. Similar results were reported for reconsolidation. However, in other cases the inhibition of UPS had no effect in memory consolidation and reconsolidation but impedes the amnesic action of protein synthesis inhibition after retrieval. The last finding was interpreted as a specific action of the UPS inhibitor on memory labilization. However, another interpretation is possible in terms of the balance between synthesis and degradation of positive and negative elements in neural plasticity, as was found in the case of long-term potentiation. To evaluate these alternative interpretations, other reconsolidation-interfering drugs than translation inhibitors should be tested. If UPS inhibitors are able to block memory impairment induced by such drugs, then the role of protein degradation in memory labilization could be confirmed beyond its effect in the synthesis/degradation balance. Here we analyzed initially the effect of UPS inhibition in a contextual conditioning task in crabs. We found that the inhibition of UPS during consolidation impaired long-term memory. In contrast, UPS inhibition did not affected memory reconsolidation after contextual retrieval but, in fact, impeded memory labilization, blocking the action of drugs that does not affect directly the protein synthesis. To extend these finding to vertebrates, we performed similar experiments in another instance of contextual conditioning, the contextual fear memory in mice. We found that the same dose of the UPS inhibitor in hippocampus did not affect memory consolidation but blocked memory labilization after retrieval. A higher dose was required to induce memory impairment during consolidation. These findings exclude alternative interpretations to the requirement of UPS in memory labilization and give evidence of this mechanism in both vertebrates and invertebrates.