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

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dc.contributor.authorLinsambarth, Sergio
dc.contributor.authorCarvajal, Francisco
dc.contributor.authorMoraga, Rodrigo
dc.contributor.authorMendez, Luis
dc.contributor.authorTamburini, Giovanni
dc.contributor.authorJimenez, Ivanka
dc.contributor.authorVerdugo, Daniel
dc.contributor.authorGómez, Gonzalo I
dc.contributor.authorJury, Nur
dc.contributor.authorMartínez, Pablo
dc.contributor.authorVan Zundert, Brigitte
dc.contributor.authorVarela, Lorena
dc.contributor.authorRetamal, Mauricio
dc.contributor.authorMartin, Claire
dc.contributor.authorAltenberg, Guillermo
dc.contributor.authorFiori, Mariana
dc.contributor.authorCerpa, Waldo
dc.contributor.authorOrellana, Juan
dc.contributor.authorStehberg, Jimmy
dc.date.accessioned2022-11-16T19:15:48Z
dc.date.available2022-11-16T19:15:48Z
dc.date.issued2021
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.es
dc.description.versionVersión publicadaes
dc.identifier.citationLinsambarth S, Carvajal FJ, Moraga-Amaro R, Mendez L, Tamburini G, Jimenez I, Verdugo DA, Gómez GI, Jury N, Martínez P, van Zundert B, Varela-Nallar L, Retamal MA, Martin C, Altenberg GA, Fiori MC, Cerpa W, Orellana JA, Stehberg J. Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala. FASEB J. 2022 Feb;36(2):e22134. doi: 10.1096/fj.202100798RRes
dc.identifier.urihttps://doi.org/10.1096/fj.202100798RRes
dc.identifier.urihttp://hdl.handle.net/11447/6679
dc.language.isoenes
dc.subjectConnexin 43 hemichannelses
dc.subjectCx43es
dc.subjectHCses
dc.subjectNMDA receptores
dc.subjectAstrocyteses
dc.subjectBasolateral amygdalaes
dc.subjectd-serinees
dc.subjectFear conditioninges
dc.subjectMemoryes
dc.subjectShort-term memoryes
dc.titleAstroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdalaes
dc.typeArticlees
dcterms.sourceThe fased journales

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