Acerca da participação da PKMZ na reconsolidação da memória de reconhecimento de objetos

Abstract

Remembering facts and events requires object recognition memory (MRO). Reconsolidation integrates new information into MRO through bidirectional changes in hippocampal synaptic efficacy and BDNF signaling. In turn, BDNF enhances long term potentiation (LTP) through protein kinase Mζ (PKMζ), which might preserve memory by controlling AMPAR function. However, the possible involvement of PKMζ in ORM reconsolidation has not yet been studied. In rats, we found that hippocampal PKMζ inhibition with zeta-inhibitory peptide (ZIP) or antisense oligonucleotides, but not PKCι/λ inhibition with ICAP, hindered retention provided MRO was reactivated simultaneously with the introduction of a novel object. Similarly, ORM reactivation increased hippocampal PKMζ only when it happened in the presence of an unfamiliar object. BDNF co-infusion reversed the amnesia induced by post-reactivation hippocampal protein synthesis inhibition but not that triggered by ZIP, which did not affect neither spontaneous oscillatory activity or CAMKII phosphorylation. Moreover, reduction of hippocampal AMPAR surface expression after MRO reactivation hampered retention, whereas blockade of AMPAR endocytosis increased PSD GluA1/GluA2 and reversed the amnesic effect of ZIP. MRO consolidation, but not reconsolidation, requires protein synthesis in entorhinal cortex (CE). We found that animals rendered amnesic by intra-CA1 ZIP reacquired MRO upon retraining, but inhibition of CE protein synthesis impaired relearning as if MRO had to be consolidated anew. Our results show that hippocampal PKMζ acts downstream BDNF to regulate AMPAR recycling at the time of reconsolidation and indicate that PKMζ inhibition during this process deletes MRO.