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...

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Principais autores: Queiroz, Claudio Marcos Teixeira de, 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.
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spelling ri-123456789-233262021-07-08T16:04:14Z Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission Queiroz, Claudio Marcos Teixeira de 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-wake cycle Intermediate sleep Acetylcholine Contextual fear conditioning Memory Neurodegenerative disorders 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. VAChTKD 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-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. 2017-06-01T12:18:59Z 2017-06-01T12:18:59Z 2013 article 1414-431X https://repositorio.ufrn.br/jspui/handle/123456789/23326 eng Acesso Aberto application/pdf
institution Repositório Institucional
collection RI - UFRN
language eng
topic Sleep-wake cycle
Intermediate sleep
Acetylcholine
Contextual fear conditioning
Memory
Neurodegenerative disorders
spellingShingle Sleep-wake cycle
Intermediate sleep
Acetylcholine
Contextual fear conditioning
Memory
Neurodegenerative disorders
Queiroz, Claudio Marcos Teixeira de
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
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. VAChTKD 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-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.
format article
author Queiroz, Claudio Marcos Teixeira de
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, Claudio Marcos Teixeira de
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, Claudio Marcos Teixeira de
title 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_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
publishDate 2017
url https://repositorio.ufrn.br/jspui/handle/123456789/23326
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