Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

Author Queiroz, Claudio Marcos Autor UNIFESP Google Scholar
Tiba, Paula Ayko Google Scholar
Moreira, Karin Monteiro Autor UNIFESP Google Scholar
Guidine, Patrícia Alves Maia Google Scholar
Rezende, Gustavo H S Google Scholar
Moraes, Márcio Flávio Dutra Google Scholar
Prado, Marco Antônio Máximo Google Scholar
Prado, Vânia Ferreira Google Scholar
Tufik, Sergio Autor UNIFESP Google Scholar
Mello, Luiz Eugenio Araujo de Moraes Autor UNIFESP Google Scholar
Institution 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
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.
Keywords Sleep-wake cycle
Intermediate sleep
Acetylcholine
Contextual fear conditioning
Memory
Neurodegenerative disorders
Language English
Date 2013-01-01
Published in Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 10, p. 844-854, 2013.
ISSN 0100-879X (Sherpa/Romeo)
Publisher Associação Brasileira de Divulgação Científica
Extent 844-854
Origin http://dx.doi.org/10.1590/1414-431X20133102
Access rights Open access Open Access
Type Article
SciELO ID S0100-879X2013001000844 (statistics in SciELO)
URI http://repositorio.unifesp.br/handle/11600/7559

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