Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?

Detalhes bibliográficos
Autor(a) principal: Carvalho Rosa, José D.
Data de Publicação: 2023
Outros Autores: Rodrigues, Nádia C., Cruz, Armando, Vaz, Sandra H., Cunha-Reis, Diana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/57692
Resumo: Copyright © 2023 Carvalho-Rosa, Rodrigues, Silva-Cruz, Vaz and Cunha-Reis. 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.
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spelling Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?BicucullineEpileptiform activityLipid raftsLong term potentiation (LTP)Low Mg2+Mesial temporal lobe epilepsy (MTLE)SeizuresCopyright © 2023 Carvalho-Rosa, Rodrigues, Silva-Cruz, Vaz and Cunha-Reis. 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.Non-epileptic seizures are identified as a common epileptogenic trigger. Early metaplasticity following seizures may contribute to epileptogenesis by abnormally altering synaptic strength and homeostatic plasticity. We now studied how in vitro epileptiform activity (EA) triggers early changes in CA1 long-term potentiation (LTP) induced by theta-burst stimulation (TBS) in rat hippocampal slices and the involvement of lipid rafts in these early metaplasticity events. Two forms of EA were induced: (1) interictal-like EA evoked by Mg2+ withdrawal and K+ elevation to 6 mM in the superfusion medium or (2) ictal-like EA induced by bicuculline (10 μM). Both EA patterns induced and LTP-like effect on CA1 synaptic transmission prior to LTP induction. LTP induced 30 min post EA was impaired, an effect more pronounced after ictal-like EA. LTP recovered to control levels 60 min post interictal-like EA but was still impaired 60 min after ictal-like EA. The synaptic molecular events underlying this altered LTP were investigated 30 min post EA in synaptosomes isolated from these slices. EA enhanced AMPA GluA1 Ser831 phosphorylation but decreased Ser845 phosphorylation and the GluA1/GluA2 ratio. Flotillin-1 and caveolin-1 were markedly decreased concomitantly with a marked increase in gephyrin levels and a less prominent increase in PSD-95. Altogether, EA differentially influences hippocampal CA1 LTP thorough regulation of GluA1/GluA2 levels and AMPA GluA1 phosphorylation suggesting that altered LTP post-seizures is a relevant target for antiepileptogenic therapies. In addition, this metaplasticity is also associated with marked alterations in classic and synaptic lipid raft markers, suggesting these may also constitute promising targets in epileptogenesis prevention.This work was supported by the national and international funding managed by the Fundação para a Ciência e a Tecnologia (FCT, IP), Portugal. Grants: FCT UIDB/04046/2020 and UIDP/04046/2020 to BioISI, PTDC/SAU-NEU/103639/2008; and FCT/POCTI (PTDC/SAU-PUB/28311/2017) EPIRaft grant to DC-R. Fellowships: SFRH/BPD/81358/2011 to DC-R and Researcher contract: Norma Transitória–DL57/2016/CP1479/CT0044 to DC-R.FrontiersRepositório da Universidade de LisboaCarvalho Rosa, José D.Rodrigues, Nádia C.Cruz, ArmandoVaz, Sandra H.Cunha-Reis, Diana2023-05-30T13:48:20Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/57692engFront Cell Neurosci . 2023 May 9;17:111769710.3389/fncel.2023.11176971662-5102info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:06:28Zoai:repositorio.ul.pt:10451/57692Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:08:12.593720Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?
title Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?
spellingShingle Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?
Carvalho Rosa, José D.
Bicuculline
Epileptiform activity
Lipid rafts
Long term potentiation (LTP)
Low Mg2+
Mesial temporal lobe epilepsy (MTLE)
Seizures
title_short Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?
title_full Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?
title_fullStr Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?
title_full_unstemmed Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?
title_sort Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?
author Carvalho Rosa, José D.
author_facet Carvalho Rosa, José D.
Rodrigues, Nádia C.
Cruz, Armando
Vaz, Sandra H.
Cunha-Reis, Diana
author_role author
author2 Rodrigues, Nádia C.
Cruz, Armando
Vaz, Sandra H.
Cunha-Reis, Diana
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Carvalho Rosa, José D.
Rodrigues, Nádia C.
Cruz, Armando
Vaz, Sandra H.
Cunha-Reis, Diana
dc.subject.por.fl_str_mv Bicuculline
Epileptiform activity
Lipid rafts
Long term potentiation (LTP)
Low Mg2+
Mesial temporal lobe epilepsy (MTLE)
Seizures
topic Bicuculline
Epileptiform activity
Lipid rafts
Long term potentiation (LTP)
Low Mg2+
Mesial temporal lobe epilepsy (MTLE)
Seizures
description Copyright © 2023 Carvalho-Rosa, Rodrigues, Silva-Cruz, Vaz and Cunha-Reis. 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.
publishDate 2023
dc.date.none.fl_str_mv 2023-05-30T13:48:20Z
2023
2023-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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url http://hdl.handle.net/10451/57692
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front Cell Neurosci . 2023 May 9;17:1117697
10.3389/fncel.2023.1117697
1662-5102
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