Wnt-5a induces the conversion of silent to functional synapses in the hippocampus

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dc.contributor.authorAlvarez-Ferradas, Carla
dc.contributor.authorWellmann, Mario
dc.contributor.authorMorales, Koyam
dc.contributor.authorFuenzalida, Marco
dc.contributor.authorCerpa, Waldo
dc.contributor.authorInestrosa, Nibaldo C.
dc.contributor.authorBonansco, Christian
dc.date.accessioned2025-01-20T21:01:30Z
dc.date.available2025-01-20T21:01:30Z
dc.date.issued2022
dc.description.abstractSynapse unsilencing is an essential mechanism for experience-dependent plasticity. Here, we showed that the application of the ligand Wnt-5a converts glutamatergic silent synapses into functional ones by increasing both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) currents (I-AMPA and I-NMDA, respectively). These effects were mimicked by the hexapeptide Foxy-5 and inhibited by secreted frizzled-related protein sFRP-2. I-NMDA potentiation was produced by increased synaptic potency, followed by an increase in the probability of release (Pr), even in the presence of 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile (CNQX). At a longer time of Wnt-5a exposure, the Pr increments were higher in I-NMDA than in I-AMPA. In the presence of NMDAR inhibitors, Wnt-5a-induced conversion was fully inhibited in 69.0% of silent synapses, whereas in the remaining synapses were converted into functional one. Our study findings showed that the Wnt-5a-activated pathway triggers AMPAR insertion into mammalian glutamatergic synapses, unsilencing non-functional synapses and promoting the formation of nascent synapses during the early postnatal development of the brain circuits.
dc.fuente.origenWOS
dc.identifier.doi10.3389/fnmol.2022.1024034
dc.identifier.issn1662-5099
dc.identifier.urihttps://doi.org/10.3389/fnmol.2022.1024034
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92898
dc.identifier.wosidWOS:000883662200001
dc.language.isoen
dc.revistaFrontiers in molecular neuroscience
dc.rightsacceso restringido
dc.subjectWnt signaling
dc.subjectsilent synapses
dc.subjecthippocampus
dc.subjectdevelopment
dc.subjectNMDA postsynaptic currents
dc.subjectAMPA receptors
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleWnt-5a induces the conversion of silent to functional synapses in the hippocampus
dc.typeartículo
dc.volumen15
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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