labilize or not to labilize? The importance of being proteasome

FUSTIÑANA, MARIA SOL; FREUDENTHAL, RAMIRO; ROMANO, ARTURO

Florencia

Congreso; 8th IBRO World Congress; 2011

International Brain Research Organization

Once a memory is consolidated, the presentation of a reminder can induce reconsolidation, a process that has inherent stages: reactivation, labilización and restabilization of the memory trace. We are studying the labilization process in two contextual associative models in phylogeneticaly distant species: context-signal memory in the crab Chasmagnathus and fear conditioning in mouse. We analysed the role of the proteasome system in memory labilization. A previous study indicated that the labilization process involved protein degradation by the proteasome. Here we found that the inhibition of the proteasome system by MG132 block labilization. Our laboratory had shown that this drug is capable to inhibit NF-kB during consolidation and the inhibition of this transcription factor results in an amnesic effect. Paradoxically, when we administered MG132 previous the re-exposure we did not find an amnesic effect on memory reconsolidation. However, when we co-injected this proteasoma inhibitor with sulfasalazine (a NF-kB inhibitor) we could not find the amnesic effect we used to obtain after sulfasalazine administration previous to the reexposure. It had been demonstrated that bicuculline, a GABA inhibitor can facilitate memory reconsolidation in the crab paradigm. Hence we co-injected bicuculline with MG132 and we were incapable to facilitate memory reconsolidation. When we co-administered MK801, a NMDA receptor inhibitor with MG132, we also coud not find the amnesic effect of MK801. All together these results indicate that proteasoma is involved in memory labilization. The hypothesis underlying is that memory labilization implies at least partial synapses retraction involving proteasoma dependent protein degradation and then stabilization during the reconsolidation process.