Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

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dc.contributor.authorQueiroz, Claudio Marcos [UNIFESP]
dc.contributor.authorTiba, Paula Ayko
dc.contributor.authorMoreira, Karin Monteiro [UNIFESP]
dc.contributor.authorGuidine, Patrícia Alves Maia
dc.contributor.authorRezende, Gustavo H S
dc.contributor.authorMoraes, Márcio Flávio Dutra
dc.contributor.authorPrado, Marco Antônio Máximo
dc.contributor.authorPrado, Vânia Ferreira
dc.contributor.authorTufik, Sergio [UNIFESP]
dc.contributor.authorMello, Luiz Eugenio Araujo de Moraes [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Federal do Rio Grande do Norte Instituto do Cerebro
dc.contributor.institutionUniversidade Federal do ABC Computacao e Cognicao Centro de Matematica
dc.contributor.institutionUniversidade Federal de Minas Gerais Departamento de Fisiologia e Biofisica Nucleo de Neurociencias
dc.contributor.institutionUniversity of Western Ontario Department of Physiology and Pharmacology and Department of Anatomy and Cell Biology Robarts Research Institute
dc.date.accessioned2015-06-14T13:45:13Z
dc.date.available2015-06-14T13:45:13Z
dc.date.issued2013-01-01
dc.description.abstractImpaired 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.en
dc.description.affiliationUniversidade Federal de São Paulo (UNIFESP) Departamento de Fisiologia
dc.description.affiliationUniversidade Federal de São Paulo (UNIFESP) Departamento de Psicobiologia
dc.description.affiliationUniversidade Federal do Rio Grande do Norte Instituto do Cerebro
dc.description.affiliationUniversidade Federal do ABC Computacao e Cognicao Centro de Matematica
dc.description.affiliationUniversidade Federal de Minas Gerais Departamento de Fisiologia e Biofisica Nucleo de Neurociencias
dc.description.affiliationUniversity of Western Ontario Department of Physiology and Pharmacology and Department of Anatomy and Cell Biology Robarts Research Institute
dc.description.affiliationUnifespUNIFESP, Depto. de Fisiologia
dc.description.affiliationUnifespUNIFESP, Depto. de Psicobiologia
dc.description.sourceSciELO
dc.format.extent844-854
dc.identifierhttp://dx.doi.org/10.1590/1414-431X20133102
dc.identifier.citationBrazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 10, p. 844-854, 2013.
dc.identifier.doi10.1590/1414-431X20133102
dc.identifier.fileS0100-879X2013001000844.pdf
dc.identifier.issn0100-879X
dc.identifier.scieloS0100-879X2013001000844
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/7559
dc.language.isoeng
dc.publisherAssociação Brasileira de Divulgação Científica
dc.relation.ispartofBrazilian Journal of Medical and Biological Research
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectSleep-wake cycleen
dc.subjectIntermediate sleepen
dc.subjectAcetylcholineen
dc.subjectContextual fear conditioningen
dc.subjectMemoryen
dc.subjectNeurodegenerative disordersen
dc.titleSleep pattern and learning in knockdown mice with reduced cholinergic neurotransmissionen
dc.typeinfo:eu-repo/semantics/article
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