Acerca da participação da PKMZ na reconsolidação da memória de reconhecimento de objetos
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...
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Μορφή: | Dissertação |
Γλώσσα: | pt_BR |
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Brasil
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Διαθέσιμο Online: | https://repositorio.ufrn.br/jspui/handle/123456789/26868 |
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Περίληψη: | 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. |
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