Papel da CaMKII hipocampal no processamento das memórias de reconhecimento de objetos

Abstract

Consolidation stabilizes learned information in long-term memories (LTM) through a protein synthesis and gene expression dependent process known as consolidation. LTM can be destabilized when recalled and must go through a “de novo” protein synthesis and gene expression dependent process called reconsolidation. Reconsolidation takes place in two phases and acts on an already existing mnemonic trace. The first phase, named destabilization, leaves the reactivated mnemonic trace in a malleable and modifiable state, while the second one, named restabilization, allows the mnemonic trace to become stable again. Object recognition memories (ORM) are declarative representations essential for remembering general knowledge and autobiographical episodes. In fact, one of the first symptoms of Alzheimer's disease is a decline in this type of memory. In recent decades, the study of hippocampal synaptic proteins has been fundamental for the better understanding of the molecular mechanisms of memory. However, the role of these proteins in ORM reconsolidation remains inconclusive. We investigated the role of hippocampal calcium/calmodulin-dependent protein kinase II (CaMKII) in ORM processing. Our results shows that in rats (1) hippocampal CaMKII is required for ORM consolidation, (2) hippocampal CaMKII activity is necessary for ORM formation in male and female, (3) inactivation of hippocampal CaMKII does not affect consolidated traces neither future learning, (4) hippocampal CaMKII activity is required for ORM destabilization, but not for ORM restabilization, (5) ORM destabilization induces phase-amplitude coupling of theta-gamma, which is blocked by CaMKII inhibition. We understand that CaMKII activity is unprecedented for physiological processes and, therefore, that the understanding of CaMKII role in memory is crucial to the better comprehension of how neurological disorders develop.