D2 dopamine receptor regulation of learning, sleep and plasticity
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/jspui/handle/123456789/19009 |
Resumo: | Dopamine and sleep have been independently linked with hippocampus-dependent learning. Since D2 dopaminergic transmission is required for the occurrence of rapid-eye-movement (REM) sleep, it is possible that dopamine affects learning by way of changes in post-acquisition REM sleep. To investigate this hypothesis, we first assessed whether D2 dopaminergic modulation in mice affects novel object preference, a hippocampus-dependent task. Animals trained in the dark period, when sleep is reduced, did not improve significantly in performance when tested 24 h after training. In contrast, animals trained in the sleep-rich light period showed significant learning after 24 h. When injected with the D2 inverse agonist haloperidol immediately after the exploration of novel objects, animals trained in the light period showed reduced novelty preference upon retesting 24 h later. Next we investigated whether haloperidol affected the protein levels of plasticity factors shown to be up-regulated in an experience-dependent manner during REM sleep. Haloperidol decreased post-exploration hippocampal protein levels at 3 h, 6 h and 12 h for phosphorylated Ca2+/calmodulin-dependent protein kinase II, at 6 h for Zif-268; and at 12 h for the brain-derived neurotrophic factor. Electrophysiological and kinematic recordings showed a significant decrease in the amount of REM sleep following haloperidol injection, while slow-wave sleep remained unaltered. Importantly, REM sleep decrease across animals was strongly correlated with deficits in novelty preference (Rho=0.56, p=0.012). Altogether, the results suggest that the dopaminergic regulation of REM sleep affects learning by modulating post-training levels of calcium-dependent plasticity factors. |
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França, A.S.C.Soares, Bruno LobãoNascimento, George Carlos doJeronimo, Selma Maria BezerraRibeiro, Sidarta Tollendal Gomes2015-04-14T13:28:41Z2015-04-14T13:28:41Z2015-01-16França AS, Lobão-Soares B, Muratori L, Nascimento G, Winne J, Pereira CM, Jeronimo SM, Ribeiro S.(2015). D2 dopamine receptor regulation of learning, sleep and plasticity. Neuropsychopharmacol. 2015 Jan 24. pii: S0924-977X(15)00012-7. doi: 10.1016/j.euroneuro.2015.01.011.0924-977Xhttps://repositorio.ufrn.br/jspui/handle/123456789/19009Dopamine and sleep have been independently linked with hippocampus-dependent learning. Since D2 dopaminergic transmission is required for the occurrence of rapid-eye-movement (REM) sleep, it is possible that dopamine affects learning by way of changes in post-acquisition REM sleep. To investigate this hypothesis, we first assessed whether D2 dopaminergic modulation in mice affects novel object preference, a hippocampus-dependent task. Animals trained in the dark period, when sleep is reduced, did not improve significantly in performance when tested 24 h after training. In contrast, animals trained in the sleep-rich light period showed significant learning after 24 h. When injected with the D2 inverse agonist haloperidol immediately after the exploration of novel objects, animals trained in the light period showed reduced novelty preference upon retesting 24 h later. Next we investigated whether haloperidol affected the protein levels of plasticity factors shown to be up-regulated in an experience-dependent manner during REM sleep. Haloperidol decreased post-exploration hippocampal protein levels at 3 h, 6 h and 12 h for phosphorylated Ca2+/calmodulin-dependent protein kinase II, at 6 h for Zif-268; and at 12 h for the brain-derived neurotrophic factor. Electrophysiological and kinematic recordings showed a significant decrease in the amount of REM sleep following haloperidol injection, while slow-wave sleep remained unaltered. Importantly, REM sleep decrease across animals was strongly correlated with deficits in novelty preference (Rho=0.56, p=0.012). Altogether, the results suggest that the dopaminergic regulation of REM sleep affects learning by modulating post-training levels of calcium-dependent plasticity factors.e Pew Latin American Fellows Program in the Biomedical Sciences, Financiadora de Estudos e Projetos (FINEP) Grant 01.06.1092.00, Ministério da Ciência, Tecnologia e Inovação (MCTI), CNPq Universal 481351/2011-6, PQ 306604/2012-4, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), FAPERN/CNPq Pronem 003/2011, Capes SticAmSud, FAPESP Center for Neuromathematics (Grant no. 2013/07699-0, São Paulo Research Foundation), Associação Alberto Santos Dumont para Apoio à Pesquisa (AASDAP), and NIMBIOS working group “Multi-scale analysis of cortical networks.”ElsevierREM sleepSono REMCaMKIIZif-268BDNFHaloperidolObject recognitionReconhecimento de objetosD2 dopamine receptor regulation of learning, sleep and plasticityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleengreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81563https://repositorio.ufrn.br/bitstream/123456789/19009/2/license.txt2fca3d993fd069474a9dfb5156c39499MD52ORIGINALD2DopamineReceptorRegulation_Franca_2015.pdfD2DopamineReceptorRegulation_Franca_2015.pdfArtigo completoapplication/pdf4560556https://repositorio.ufrn.br/bitstream/123456789/19009/1/D2DopamineReceptorRegulation_Franca_2015.pdf59afbb984d55bb28c9502926a6ca06f7MD51TEXTArthurFrança_ICE_2015_D2 dopamine receptor.pdf.txtArthurFrança_ICE_2015_D2 dopamine receptor.pdf.txtExtracted texttext/plain57476https://repositorio.ufrn.br/bitstream/123456789/19009/7/ArthurFran%c3%a7a_ICE_2015_D2%20dopamine%20receptor.pdf.txt95981c696e6a480e39e287675a4be753MD57THUMBNAILArthurFrança_ICE_2015_D2 dopamine receptor.pdf.jpgArthurFrança_ICE_2015_D2 dopamine receptor.pdf.jpgIM Thumbnailimage/jpeg8631https://repositorio.ufrn.br/bitstream/123456789/19009/8/ArthurFran%c3%a7a_ICE_2015_D2%20dopamine%20receptor.pdf.jpgb13c9d6e55e34d26acbe8a9fe94defa8MD58123456789/190092021-11-09 16:05:14.302oai:https://repositorio.ufrn.br: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ório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2021-11-09T19:05:14Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.fl_str_mv |
D2 dopamine receptor regulation of learning, sleep and plasticity |
title |
D2 dopamine receptor regulation of learning, sleep and plasticity |
spellingShingle |
D2 dopamine receptor regulation of learning, sleep and plasticity França, A.S.C. REM sleep Sono REM CaMKII Zif-268 BDNF Haloperidol Object recognition Reconhecimento de objetos |
title_short |
D2 dopamine receptor regulation of learning, sleep and plasticity |
title_full |
D2 dopamine receptor regulation of learning, sleep and plasticity |
title_fullStr |
D2 dopamine receptor regulation of learning, sleep and plasticity |
title_full_unstemmed |
D2 dopamine receptor regulation of learning, sleep and plasticity |
title_sort |
D2 dopamine receptor regulation of learning, sleep and plasticity |
author |
França, A.S.C. |
author_facet |
França, A.S.C. Soares, Bruno Lobão Nascimento, George Carlos do Jeronimo, Selma Maria Bezerra Ribeiro, Sidarta Tollendal Gomes |
author_role |
author |
author2 |
Soares, Bruno Lobão Nascimento, George Carlos do Jeronimo, Selma Maria Bezerra Ribeiro, Sidarta Tollendal Gomes |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
França, A.S.C. Soares, Bruno Lobão Nascimento, George Carlos do Jeronimo, Selma Maria Bezerra Ribeiro, Sidarta Tollendal Gomes |
dc.subject.por.fl_str_mv |
REM sleep Sono REM CaMKII Zif-268 BDNF Haloperidol Object recognition Reconhecimento de objetos |
topic |
REM sleep Sono REM CaMKII Zif-268 BDNF Haloperidol Object recognition Reconhecimento de objetos |
description |
Dopamine and sleep have been independently linked with hippocampus-dependent learning. Since D2 dopaminergic transmission is required for the occurrence of rapid-eye-movement (REM) sleep, it is possible that dopamine affects learning by way of changes in post-acquisition REM sleep. To investigate this hypothesis, we first assessed whether D2 dopaminergic modulation in mice affects novel object preference, a hippocampus-dependent task. Animals trained in the dark period, when sleep is reduced, did not improve significantly in performance when tested 24 h after training. In contrast, animals trained in the sleep-rich light period showed significant learning after 24 h. When injected with the D2 inverse agonist haloperidol immediately after the exploration of novel objects, animals trained in the light period showed reduced novelty preference upon retesting 24 h later. Next we investigated whether haloperidol affected the protein levels of plasticity factors shown to be up-regulated in an experience-dependent manner during REM sleep. Haloperidol decreased post-exploration hippocampal protein levels at 3 h, 6 h and 12 h for phosphorylated Ca2+/calmodulin-dependent protein kinase II, at 6 h for Zif-268; and at 12 h for the brain-derived neurotrophic factor. Electrophysiological and kinematic recordings showed a significant decrease in the amount of REM sleep following haloperidol injection, while slow-wave sleep remained unaltered. Importantly, REM sleep decrease across animals was strongly correlated with deficits in novelty preference (Rho=0.56, p=0.012). Altogether, the results suggest that the dopaminergic regulation of REM sleep affects learning by modulating post-training levels of calcium-dependent plasticity factors. |
publishDate |
2015 |
dc.date.accessioned.fl_str_mv |
2015-04-14T13:28:41Z |
dc.date.available.fl_str_mv |
2015-04-14T13:28:41Z |
dc.date.issued.fl_str_mv |
2015-01-16 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
França AS, Lobão-Soares B, Muratori L, Nascimento G, Winne J, Pereira CM, Jeronimo SM, Ribeiro S.(2015). D2 dopamine receptor regulation of learning, sleep and plasticity. Neuropsychopharmacol. 2015 Jan 24. pii: S0924-977X(15)00012-7. doi: 10.1016/j.euroneuro.2015.01.011. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/jspui/handle/123456789/19009 |
dc.identifier.issn.none.fl_str_mv |
0924-977X |
identifier_str_mv |
França AS, Lobão-Soares B, Muratori L, Nascimento G, Winne J, Pereira CM, Jeronimo SM, Ribeiro S.(2015). D2 dopamine receptor regulation of learning, sleep and plasticity. Neuropsychopharmacol. 2015 Jan 24. pii: S0924-977X(15)00012-7. doi: 10.1016/j.euroneuro.2015.01.011. 0924-977X |
url |
https://repositorio.ufrn.br/jspui/handle/123456789/19009 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Elsevier |
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Elsevier |
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reponame:Repositório Institucional da UFRN instname:Universidade Federal do Rio Grande do Norte (UFRN) instacron:UFRN |
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Universidade Federal do Rio Grande do Norte (UFRN) |
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UFRN |
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UFRN |
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Repositório Institucional da UFRN |
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