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Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

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 co...

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Autores principales: Queiroz, C.M., Tiba, P.A., Moreira, K.M., Guidine, P.A.M., Rezende, G.H.S., Moraes, M.F.D., Prado, M.A.M., Prado, V.F., Tufik, S., Mello, L.E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Associação Brasileira de Divulgação Científica 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854314/
https://www.ncbi.nlm.nih.gov/pubmed/24141612
http://dx.doi.org/10.1590/1414-431X20133102
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author Queiroz, C.M.
Tiba, P.A.
Moreira, K.M.
Guidine, P.A.M.
Rezende, G.H.S.
Moraes, M.F.D.
Prado, M.A.M.
Prado, V.F.
Tufik, S.
Mello, L.E.
author_facet Queiroz, C.M.
Tiba, P.A.
Moreira, K.M.
Guidine, P.A.M.
Rezende, G.H.S.
Moraes, M.F.D.
Prado, M.A.M.
Prado, V.F.
Tufik, S.
Mello, L.E.
author_sort Queiroz, C.M.
collection PubMed
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-KD(HET), 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-KD(HET) 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-KD(HET) 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-KD(HET) 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-KD(HET) mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.
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spelling pubmed-38543142013-12-16 Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission Queiroz, C.M. Tiba, P.A. Moreira, K.M. Guidine, P.A.M. Rezende, G.H.S. Moraes, M.F.D. Prado, M.A.M. Prado, V.F. Tufik, S. Mello, L.E. Braz J Med Biol Res Biomedical Sciences 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-KD(HET), 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-KD(HET) 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-KD(HET) 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-KD(HET) 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-KD(HET) mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders. Associação Brasileira de Divulgação Científica 2013-10-02 /pmc/articles/PMC3854314/ /pubmed/24141612 http://dx.doi.org/10.1590/1414-431X20133102 Text en http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedical Sciences
Queiroz, C.M.
Tiba, P.A.
Moreira, K.M.
Guidine, P.A.M.
Rezende, G.H.S.
Moraes, M.F.D.
Prado, M.A.M.
Prado, V.F.
Tufik, S.
Mello, L.E.
Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission
title 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_short Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission
title_sort sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission
topic Biomedical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854314/
https://www.ncbi.nlm.nih.gov/pubmed/24141612
http://dx.doi.org/10.1590/1414-431X20133102
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