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Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine

2023Artigo científico Acesso aberto
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dc.contributor.authorAbreu, Daniela Sofia
dc.contributor.authorGomes, Joana I.
dc.contributor.authorRibeiro, Filipa
dc.contributor.authorDiógenes, Maria José
dc.contributor.authorSebastião, Ana M
dc.contributor.authorVaz, Sandra H.
dc.date.accessioned2025-06-12T14:10:37Z
dc.date.available2025-06-12T14:10:37Z
dc.date.issued2023
dc.descriptionCopyright © 2023 Abreu, Gomes, Ribeiro, Diógenes, Sebastião and Vaz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.pt_PT
dc.description.abstractAstrocytes, the most abundant glial cells in the central nervous system (CNS), sense synaptic activity and respond through the release of gliotransmitters, a process mediated by intracellular Ca2+ level changes and SNARE-dependent mechanisms. Ionotropic N-methyl-D-aspartate (NMDA) receptors, which are activated by glutamate along with D-serine or glycine, play a crucial role in learning, memory, and synaptic plasticity. However, the precise impact of astrocyte-released D-serine on neuronal modulation remains insufficiently characterized. To address this, we have used the dominant negative SNARE (dnSNARE) mouse model, which selectively inhibits SNARE-dependent exocytosis from astrocytes. We recorded field excitatory postsynaptic potentials (fEPSPs) in CA3-CA1 synapses within hippocampal slices obtained from dnSNARE mice and wild-type (Wt) littermates. Our results demonstrate that hippocampal θ-burst long-term potentiation (LTP), a critical form of synaptic plasticity, is impaired in hippocampal slices from dnSNARE mice. Notably, this LTP impairment was rescued upon incubation with D-serine. To further investigate the involvement of astrocytes in D-serine-mediated mechanisms of LTP maintenance, we perfused hippocampal slices with L-serine - a substrate used by both neurons and astrocytes for D-serine production. The enhancement in LTP observed in dnSNARE mice was exclusively associated with D-serine presence, with no effects evident in the presence of L-serine. Additionally, both D- and L-serine reduced basal synaptic strength in the hippocampal slices of both Wt and dnSNARE mice. These results provide compelling evidence that distinct processes underlie the modulation of basal synaptic transmission and LTP through D-serine. Our findings underscore the pivotal contribution of astrocytes in D-serine-mediated processes that govern LTP establishment and basal transmission. This study not only provides essential insights into the intricate interplay between neurons and astrocytes but also emphasizes their collective role in shaping hippocampal synaptic function.pt_PT
dc.description.sponsorshipThe author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by project funding from Fundação para a Ciência e para a Tecnologia (FCT) to AMS (PTDC/MEDFAR/30933/2017) and SHV (PTDC/BTM-SAL/32147/2017). This project has received funding from H2020-WIDESPREAD-05- 2017-Twinning (EpiEpinet) under grant agreement No. 952455 and the ISN Career Development Grant 2021 to SHV The authors are grateful to Professor Philip Haydon and Dr. João Oliveira for sharing the dn-SNARE mouse lines. The authors acknowledge the Fundação para a Ciência e Tecnologia (FCT) post-doctoral fellowship (PTDC/BTM-SAL/32147/2017-IMM/CT/35-2018) to FFR.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Cell Neurosci. 2023 Dec 7:17:1282841pt_PT
dc.identifier.doi10.3389/fncel.2023.1282841pt_PT
dc.identifier.eissn1662-5102
dc.identifier.urihttp://hdl.handle.net/10400.5/101537
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relationPTDC/MEDFAR/30933/2017pt_PT
dc.relationEpileptogenesis and Epilepsy Network: from genes, synapses and circuits to pave the way for novel drugs and strategies
dc.relationAstrosomes: Artificial Astrocytes as a Novel Approach to Regulate Neuronal Communication
dc.relation.publisherversionhttps://www.frontiersin.org/journals/cellular-neurosciencept_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAstrocytept_PT
dc.subjectD-serinept_PT
dc.subjectGliotransmissionpt_PT
dc.subjectSynaptic plasticitypt_PT
dc.subjectTripartite synapsept_PT
dc.titleAstrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serinept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleEpileptogenesis and Epilepsy Network: from genes, synapses and circuits to pave the way for novel drugs and strategies
oaire.awardTitleAstrosomes: Artificial Astrocytes as a Novel Approach to Regulate Neuronal Communication
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/952455/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBTM-SAL%2F32147%2F2017/PT
oaire.citation.titleFrontiers in Cellular Neurosciencept_PT
oaire.citation.volume17pt_PT
oaire.fundingStreamH2020
oaire.fundingStream3599-PPCDT
person.familyNameda Costa Abreu
person.familyNameGomes
person.familyNameRibeiro
person.familyNamede Oliveira Diógenes Nogueira
person.familyNameSebastião
person.familyNameHenriques Vaz
person.givenNameDaniela Sofia
person.givenNameJoana I.
person.givenNameFilipa
person.givenNameMaria José
person.givenNameAna M
person.givenNameSandra Cristina
person.identifier694933
person.identifier.ciencia-idE018-22E1-F4B3
person.identifier.ciencia-id7A17-D40A-D6F5
person.identifier.ciencia-id6916-485D-36C3
person.identifier.ciencia-id4B10-886B-DAFC
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.ciencia-id0E1C-952D-61BE
person.identifier.orcid0000-0002-6579-3596
person.identifier.orcid0000-0001-7761-1983
person.identifier.orcid0000-0002-4006-7328
person.identifier.orcid0000-0001-5486-6246
person.identifier.orcid0000-0001-9030-6115
person.identifier.orcid0000-0003-4258-9397
person.identifier.ridS-1079-2018
person.identifier.scopus-author-id7004409879
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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