Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

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dc.contributor.author Queiroz, Claudio Marcos [UNIFESP]
dc.contributor.author Tiba, Paula Ayko
dc.contributor.author Moreira, Karin Monteiro [UNIFESP]
dc.contributor.author Guidine, Patrícia Alves Maia
dc.contributor.author Rezende, Gustavo H S
dc.contributor.author Moraes, Márcio Flávio Dutra
dc.contributor.author Prado, Marco Antônio Máximo
dc.contributor.author Prado, Vânia Ferreira
dc.contributor.author Tufik, Sergio [UNIFESP]
dc.contributor.author Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]
dc.date.accessioned 2015-06-14T13:45:13Z
dc.date.available 2015-06-14T13:45:13Z
dc.date.issued 2013-01-01
dc.identifier http://dx.doi.org/10.1590/1414-431X20133102
dc.identifier.citation Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 10, p. 844-854, 2013.
dc.identifier.issn 0100-879X
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/7559
dc.description.abstract 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. en
dc.format.extent 844-854
dc.language.iso eng
dc.publisher Associação Brasileira de Divulgação Científica
dc.relation.ispartof Brazilian Journal of Medical and Biological Research
dc.rights Acesso aberto
dc.subject Sleep-wake cycle en
dc.subject Intermediate sleep en
dc.subject Acetylcholine en
dc.subject Contextual fear conditioning en
dc.subject Memory en
dc.subject Neurodegenerative disorders en
dc.title Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Universidade Federal do Rio Grande do Norte Instituto do Cerebro
dc.contributor.institution Universidade Federal do ABC Computacao e Cognicao Centro de Matematica
dc.contributor.institution Universidade Federal de Minas Gerais Departamento de Fisiologia e Biofisica Nucleo de Neurociencias
dc.contributor.institution University of Western Ontario Department of Physiology and Pharmacology and Department of Anatomy and Cell Biology Robarts Research Institute
dc.description.affiliation Universidade Federal de São Paulo (UNIFESP) Departamento de Fisiologia
dc.description.affiliation Universidade Federal de São Paulo (UNIFESP) Departamento de Psicobiologia
dc.description.affiliation Universidade Federal do Rio Grande do Norte Instituto do Cerebro
dc.description.affiliation Universidade Federal do ABC Computacao e Cognicao Centro de Matematica
dc.description.affiliation Universidade Federal de Minas Gerais Departamento de Fisiologia e Biofisica Nucleo de Neurociencias
dc.description.affiliation University of Western Ontario Department of Physiology and Pharmacology and Department of Anatomy and Cell Biology Robarts Research Institute
dc.description.affiliationUnifesp UNIFESP, Depto. de Fisiologia
dc.description.affiliationUnifesp UNIFESP, Depto. de Psicobiologia
dc.identifier.file S0100-879X2013001000844.pdf
dc.identifier.scielo S0100-879X2013001000844
dc.identifier.doi 10.1590/1414-431X20133102
dc.description.source SciELO



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