Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala

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dc.article.numbere22134
dc.catalogadorgjm
dc.contributor.authorLinsambarth, Sergio
dc.contributor.authorCarvajal Cachaña, Francisco Javier
dc.contributor.authorMoraga Amaro, Rodrigo
dc.contributor.authorMendez, Luis
dc.contributor.authorTamburini, Giovanni
dc.contributor.authorJimenez, Ivanka
dc.contributor.authorAntonio Verdugo, Daniel
dc.contributor.authorGomez, Gonzalo, I
dc.contributor.authorJury, Nur
dc.contributor.authorMartinez, Pablo
dc.contributor.authorvan Zundert, Brigitte
dc.contributor.authorVarela Nallar, Lorena
dc.contributor.authorRetamal, Mauricio A.
dc.contributor.authorMartin, Claire
dc.contributor.authorAltenberg, Guillermo A.
dc.contributor.authorFiori, Mariana C.
dc.contributor.authorCerpa Nebott, Waldo Francisco
dc.contributor.authorOrellana Roca, Juan Andrés
dc.contributor.authorStehberg, Jimmy
dc.date.accessioned2024-10-16T14:30:09Z
dc.date.available2024-10-16T14:30:09Z
dc.date.issued2022
dc.description.abstractAstrocytes release gliotransmitters via connexin 43 (Cx43) hemichannels into neighboring synapses, which can modulate synaptic activity and are necessary for fear memory consolidation. However, the gliotransmitters released, and their mechanisms of action remain elusive. Here, we report that fear conditioning training elevated Cx43 hemichannel activity in astrocytes from the basolateral amygdala (BLA). The selective blockade of Cx43 hemichannels by microinfusion of TAT-Cx43L2 peptide into the BLA induced memory deficits 1 and 24 h after training, without affecting learning. The memory impairments were prevented by the co-injection of glutamate and D-serine, but not by the injection of either alone, suggesting a role for NMDA receptors (NMDAR). The incubation with TAT-Cx43L2 decreased NMDAR-mediated currents in BLA slices, effect that was also prevented by the addition of glutamate and D-serine. NMDARs in primary neuronal cultures were unaffected by TAT-Cx43L2, ruling out direct effects of the peptide on NMDARs. Finally, we show that D-serine permeates through purified Cx43 hemichannels reconstituted in liposomes. We propose that the release of glutamate and D-serine from astrocytes through Cx43 hemichannels is necessary for the activation of post-synaptic NMDARs during training, to allow for the formation of short-term and subsequent long-term memory, but not for learning per se.
dc.description.funderUNAB
dc.description.funderFONDECYT
dc.description.funderCORFO INNOVA
dc.description.funderFONDEQUIP EQM
dc.description.funderECOS-CONICYT
dc.description.funderPrograma de Investigacion Asociativa (PIA): Grant Anillo de Ciencia y Tecnologia
dc.description.funderBMBF
dc.description.funderProyecto interno Universidad del Desarrollo
dc.format.extent18 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1096/fj.202100798RR
dc.identifier.eissn1530-6860
dc.identifier.issn0892-6638
dc.identifier.pubmedidMEDLINE:35061296
dc.identifier.urihttps://doi.org/10.1096/fj.202100798RR
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/88254
dc.identifier.wosidWOS:000747987800047
dc.information.autorucFacultad de Ciencias Biológicas; Carvajal Cachaña, Francisco Javier; S/I; 237252
dc.information.autorucFacultad de Ciencias Biológicas; Cerpa Nebott, Waldo Francisco; 0000-0001-7344-0144; 16584
dc.information.autorucEscuela de Medicina; Orellana Roca, Juan Andrés; 0000-0003-4076-207X; 126007
dc.issue.numero2
dc.language.isoen
dc.nota.accesocontenido parcial
dc.revistaThe FASEB Journal
dc.rightsacceso restringido
dc.subjectAstrocytes
dc.subjectBasolateral amygdala
dc.subjectConnexin 43 hemichannels
dc.subjectCx43
dc.subjectD-serine
dc.subjectFear conditioning
dc.subjectHCs
dc.subjectMemory
dc.subjectNMDA receptor
dc.subjectShort-term memory
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleAstroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala
dc.typeartículo
dc.volumen36
sipa.codpersvinculados237252
sipa.codpersvinculados16584
sipa.codpersvinculados126007
sipa.trazabilidadORCID;2024-10-14
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