Mecanismos neurais envolvidos na formação, atualização e integração da memória de reconhecimento de objetos

Abstract

New memories are unstable and susceptible to interference. Most of them are transient and only a few are stored as long-term entities through consolidation, a protein synthesisdependent stabilization process. Long-term memories can become unstable again when recalled and, to persist, they must be reconsolidated. Reconsolidation is also a stabilization process that depends on protein synthesis, but it is not a mere repetition of consolidation. The biological relevance of memory reconsolidation is still under debate, but evidence suggests that it would serve to update consolidated memories with new information acquired during recall. Object recognition memory (ORM) is a component of declarative memories that allows animals to discriminate between familiar and new items. In this work, we used Wistar rats to confirm the participation of the dorsal hippocampus in ORM consolidation and show that their underlying molecular mechanisms store independent representations. We also confirmed that ORM reconsolidation is hippocampus-dependent only when a novel object is perceived during reactivation and demonstrated that this process mediates incorporation of information concerning that new object into the original memory trace. In addition, we showed that ORM update is driven by D1/D5 dopamine receptor activity and involves synaptic plasticity controlled by Zif268, BDNF and PKMζ-regulated AMPA receptor recycling in the dorsal hippocampus. We also found that ORM destabilization is associated with theta-gamma phase amplitude coupling in the hippocampus, and that artificial induction of this oscillatory pattern can destabilize memories that are normally resistant to reconsolidation. Finally, we showed that the amnesia observed after reconsolidation disruption is not due to retrieval failure, but to elimination of the reactivated trace, and that memories that are part of a mnemonic network are susceptible to reconsolidation by indirect reactivation.