A requirement for epigenetic modifications during noradrenergic stabilization of heterosynaptic LTP in the hippocampus.
Neurobiol Learn Mem
; 161: 72-82, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30930287
ABSTRACT
Beta-adrenergic receptor (b-AR) activation by noradrenaline (NA) enhances memory formation and long-term potentiation (LTP), a form of synaptic plasticity characterized by an activity-dependent increase in synaptic strength. LTP is believed to be a cellular mechanism for contextual learning and memory. In the mammalian hippocampus, LTP can be observed at multiple synaptic pathways after strong stimulation of a single synaptic pathway. This heterosynaptic LTP is believed to involve synaptic tagging of active synapses and capture of plasticity-related proteins that enable heterosynaptic transfer of persistent potentiation. These processes may permit distinct neural pathways to associate information transmitted by separate, but convergent, synaptic inputs. We had previously shown that transcription and epigenetic modifications were necessary for stabilization of homosynaptic LTP. However, it is unclear whether transfer of LTP to a second, heterosynaptic pathway involves b-ARs signalling to the nucleus. Using electrophysiologic recordings in area CA1 of murine hippocampal slices, we show here that pharmacologically inhibiting b-AR activation, transcription, DNA methyltransferase or histone acetyltransferase activation, prevents stabilization of heterosynaptic LTP. Our data suggest that noradrenergic stabilization of heterosynaptic ("tagged") LTP requires not only transcription, but specifically, DNA methylation and histone acetylation. NA promotes stable heterosynaptic plasticity through engagement of nuclear processes that may contribute to prompt consolidation of short-term memories into resilient long-term memories under conditions when the brain's noradrenergic system is recruited.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Norepinefrina
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Receptores Adrenérgicos beta
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Potenciação de Longa Duração
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Potenciais Pós-Sinápticos Excitadores
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Epigênese Genética
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Região CA1 Hipocampal
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article