Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/7559 http://dx.doi.org/10.1590/1414-431X20133102 |
Resumo: | Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT) system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively), which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders. |
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Queiroz, Claudio Marcos [UNIFESP]Tiba, Paula AykoMoreira, Karin Monteiro [UNIFESP]Guidine, Patrícia Alves MaiaRezende, Gustavo H SMoraes, Márcio Flávio DutraPrado, Marco Antônio MáximoPrado, Vânia FerreiraTufik, Sergio [UNIFESP]Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Universidade Federal do Rio Grande do Norte Instituto do CerebroUniversidade Federal do ABC Computacao e Cognicao Centro de MatematicaUniversidade Federal de Minas Gerais Departamento de Fisiologia e Biofisica Nucleo de NeurocienciasUniversity of Western Ontario Department of Physiology and Pharmacology and Department of Anatomy and Cell Biology Robarts Research Institute2015-06-14T13:45:13Z2015-06-14T13:45:13Z2013-01-01Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 10, p. 844-854, 2013.0100-879Xhttp://repositorio.unifesp.br/handle/11600/7559http://dx.doi.org/10.1590/1414-431X20133102S0100-879X2013001000844.pdfS0100-879X201300100084410.1590/1414-431X20133102Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT) system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively), which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.Universidade Federal de São Paulo (UNIFESP) Departamento de FisiologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUniversidade Federal do Rio Grande do Norte Instituto do CerebroUniversidade Federal do ABC Computacao e Cognicao Centro de MatematicaUniversidade Federal de Minas Gerais Departamento de Fisiologia e Biofisica Nucleo de NeurocienciasUniversity of Western Ontario Department of Physiology and Pharmacology and Department of Anatomy and Cell Biology Robarts Research InstituteUNIFESP, Depto. de FisiologiaUNIFESP, Depto. de PsicobiologiaSciELO844-854engAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological ResearchSleep-wake cycleIntermediate sleepAcetylcholineContextual fear conditioningMemoryNeurodegenerative disordersSleep pattern and learning in knockdown mice with reduced cholinergic neurotransmissioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALS0100-879X2013001000844.pdfapplication/pdf1082411${dspace.ui.url}/bitstream/11600/7559/1/S0100-879X2013001000844.pdfbd4e56e4779c8f11e3dfd966bf76033fMD51open accessTEXTS0100-879X2013001000844.pdf.txtS0100-879X2013001000844.pdf.txtExtracted texttext/plain45792${dspace.ui.url}/bitstream/11600/7559/2/S0100-879X2013001000844.pdf.txt8c84aea1967042ea8d8d497bcec4d7b3MD52open access11600/75592021-09-30 17:25:18.411open accessoai:repositorio.unifesp.br:11600/7559Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652021-09-30T20:25:18Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission |
title |
Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission |
spellingShingle |
Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission Queiroz, Claudio Marcos [UNIFESP] Sleep-wake cycle Intermediate sleep Acetylcholine Contextual fear conditioning Memory Neurodegenerative disorders |
title_short |
Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission |
title_full |
Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission |
title_fullStr |
Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission |
title_full_unstemmed |
Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission |
title_sort |
Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission |
author |
Queiroz, Claudio Marcos [UNIFESP] |
author_facet |
Queiroz, Claudio Marcos [UNIFESP] Tiba, Paula Ayko Moreira, Karin Monteiro [UNIFESP] Guidine, Patrícia Alves Maia Rezende, Gustavo H S Moraes, Márcio Flávio Dutra Prado, Marco Antônio Máximo Prado, Vânia Ferreira Tufik, Sergio [UNIFESP] Mello, Luiz Eugenio Araujo de Moraes [UNIFESP] |
author_role |
author |
author2 |
Tiba, Paula Ayko Moreira, Karin Monteiro [UNIFESP] Guidine, Patrícia Alves Maia Rezende, Gustavo H S Moraes, Márcio Flávio Dutra Prado, Marco Antônio Máximo Prado, Vânia Ferreira Tufik, Sergio [UNIFESP] Mello, Luiz Eugenio Araujo de Moraes [UNIFESP] |
author2_role |
author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Universidade Federal do Rio Grande do Norte Instituto do Cerebro Universidade Federal do ABC Computacao e Cognicao Centro de Matematica Universidade Federal de Minas Gerais Departamento de Fisiologia e Biofisica Nucleo de Neurociencias University of Western Ontario Department of Physiology and Pharmacology and Department of Anatomy and Cell Biology Robarts Research Institute |
dc.contributor.author.fl_str_mv |
Queiroz, Claudio Marcos [UNIFESP] Tiba, Paula Ayko Moreira, Karin Monteiro [UNIFESP] Guidine, Patrícia Alves Maia Rezende, Gustavo H S Moraes, Márcio Flávio Dutra Prado, Marco Antônio Máximo Prado, Vânia Ferreira Tufik, Sergio [UNIFESP] Mello, Luiz Eugenio Araujo de Moraes [UNIFESP] |
dc.subject.eng.fl_str_mv |
Sleep-wake cycle Intermediate sleep Acetylcholine Contextual fear conditioning Memory Neurodegenerative disorders |
topic |
Sleep-wake cycle Intermediate sleep Acetylcholine Contextual fear conditioning Memory Neurodegenerative disorders |
description |
Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT) system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively), which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-01-01 |
dc.date.accessioned.fl_str_mv |
2015-06-14T13:45:13Z |
dc.date.available.fl_str_mv |
2015-06-14T13:45:13Z |
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 |
Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 10, p. 844-854, 2013. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/7559 http://dx.doi.org/10.1590/1414-431X20133102 |
dc.identifier.issn.none.fl_str_mv |
0100-879X |
dc.identifier.file.none.fl_str_mv |
S0100-879X2013001000844.pdf |
dc.identifier.scielo.none.fl_str_mv |
S0100-879X2013001000844 |
dc.identifier.doi.none.fl_str_mv |
10.1590/1414-431X20133102 |
identifier_str_mv |
Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 10, p. 844-854, 2013. 0100-879X S0100-879X2013001000844.pdf S0100-879X2013001000844 10.1590/1414-431X20133102 |
url |
http://repositorio.unifesp.br/handle/11600/7559 http://dx.doi.org/10.1590/1414-431X20133102 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
844-854 |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP |
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