EphA4 is involved in sleep regulation but not in the electrophysiological response to sleep deprivation

Marlène Freyburger, Audrey Pierre, Gabrielle Paquette, Erika Bélanger-Nelson, Joseph Bedont, Pierre Olivier Gaudreault, Guy Drolet, Sylvie Laforest, Seth Blackshaw, Nicolas Cermakian, Guy Doucet, Valérie Mongrain

Research output: Contribution to journalArticle

Abstract

Study Objectives: Optimal sleep is ensured by the interaction of circadian and homeostatic processes. Although synaptic plasticity seems to contribute to both processes, the specific players involved are not well understood. The EphA4 tyrosine kinase receptor is a cell adhesion protein regulating synaptic plasticity. We investigated the role of EphA4 in sleep regulation using electrocorticography in mice lacking EphA4 and gene expression measurements. Methods: EphA4 knockout (KO) mice, ClockΔ19/Δ19 mutant mice and littermates, C57BL/6J and CD-1 mice, and Sprague-Dawley rats were studied under a 12 h light: 12 h dark cycle, under undisturbed conditions or 6 h sleep deprivation (SLD), and submitted to a 48 h electrophysiological recording and/or brain sampling at different time of day. Results: EphA4 KO mice showed less rapid eye movement sleep (REMS), enhanced duration of individual bouts of wakefulness and nonrapid eye movement sleep (NREMS) during the light period, and a blunted daily rhythm of NREMS sigma activity. The NREMS delta activity response to SLD was unchanged in EphA4 KO mice. However, SLD increased EphA4 expression in the thalamic/hypothalamic region in C57BL/6J mice. We further show the presence of E-boxes in the promoter region of EphA4, a lower expression of EphA4 in Clock mutant mice, a rhythmic expression of EphA4 ligands in several brain areas, expression of EphA4 in the suprachiasmatic nuclei of the hypothalamus (SCN), and finally an unchanged number of cells expressing Vip, Grp and Avp in the SCN of EphA4 KO mice. Conclusions: Our results suggest that EphA4 is involved in circadian sleep regulation.

Original languageEnglish (US)
Pages (from-to)613-624
Number of pages12
JournalSleep
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Sleep Deprivation
Sleep
Knockout Mice
Eye Movements
Suprachiasmatic Nucleus
Neuronal Plasticity
Inbred C57BL Mouse
Hypothalamus
Light
Wakefulness
REM Sleep
Brain
Receptor Protein-Tyrosine Kinases
Genetic Promoter Regions
Cell Adhesion
Sprague Dawley Rats
Cell Count
Ligands
Gene Expression

Keywords

  • Delta activity
  • Gene expression
  • Rapid eye movement sleep
  • Sigma activity
  • Suprachiasmatic nuclei

ASJC Scopus subject areas

  • Physiology (medical)
  • Clinical Neurology

Cite this

Freyburger, M., Pierre, A., Paquette, G., Bélanger-Nelson, E., Bedont, J., Gaudreault, P. O., ... Mongrain, V. (2016). EphA4 is involved in sleep regulation but not in the electrophysiological response to sleep deprivation. Sleep, 39(3), 613-624. https://doi.org/10.5665/sleep.5538

EphA4 is involved in sleep regulation but not in the electrophysiological response to sleep deprivation. / Freyburger, Marlène; Pierre, Audrey; Paquette, Gabrielle; Bélanger-Nelson, Erika; Bedont, Joseph; Gaudreault, Pierre Olivier; Drolet, Guy; Laforest, Sylvie; Blackshaw, Seth; Cermakian, Nicolas; Doucet, Guy; Mongrain, Valérie.

In: Sleep, Vol. 39, No. 3, 01.03.2016, p. 613-624.

Research output: Contribution to journalArticle

Freyburger, M, Pierre, A, Paquette, G, Bélanger-Nelson, E, Bedont, J, Gaudreault, PO, Drolet, G, Laforest, S, Blackshaw, S, Cermakian, N, Doucet, G & Mongrain, V 2016, 'EphA4 is involved in sleep regulation but not in the electrophysiological response to sleep deprivation', Sleep, vol. 39, no. 3, pp. 613-624. https://doi.org/10.5665/sleep.5538
Freyburger M, Pierre A, Paquette G, Bélanger-Nelson E, Bedont J, Gaudreault PO et al. EphA4 is involved in sleep regulation but not in the electrophysiological response to sleep deprivation. Sleep. 2016 Mar 1;39(3):613-624. https://doi.org/10.5665/sleep.5538
Freyburger, Marlène ; Pierre, Audrey ; Paquette, Gabrielle ; Bélanger-Nelson, Erika ; Bedont, Joseph ; Gaudreault, Pierre Olivier ; Drolet, Guy ; Laforest, Sylvie ; Blackshaw, Seth ; Cermakian, Nicolas ; Doucet, Guy ; Mongrain, Valérie. / EphA4 is involved in sleep regulation but not in the electrophysiological response to sleep deprivation. In: Sleep. 2016 ; Vol. 39, No. 3. pp. 613-624.
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abstract = "Study Objectives: Optimal sleep is ensured by the interaction of circadian and homeostatic processes. Although synaptic plasticity seems to contribute to both processes, the specific players involved are not well understood. The EphA4 tyrosine kinase receptor is a cell adhesion protein regulating synaptic plasticity. We investigated the role of EphA4 in sleep regulation using electrocorticography in mice lacking EphA4 and gene expression measurements. Methods: EphA4 knockout (KO) mice, ClockΔ19/Δ19 mutant mice and littermates, C57BL/6J and CD-1 mice, and Sprague-Dawley rats were studied under a 12 h light: 12 h dark cycle, under undisturbed conditions or 6 h sleep deprivation (SLD), and submitted to a 48 h electrophysiological recording and/or brain sampling at different time of day. Results: EphA4 KO mice showed less rapid eye movement sleep (REMS), enhanced duration of individual bouts of wakefulness and nonrapid eye movement sleep (NREMS) during the light period, and a blunted daily rhythm of NREMS sigma activity. The NREMS delta activity response to SLD was unchanged in EphA4 KO mice. However, SLD increased EphA4 expression in the thalamic/hypothalamic region in C57BL/6J mice. We further show the presence of E-boxes in the promoter region of EphA4, a lower expression of EphA4 in Clock mutant mice, a rhythmic expression of EphA4 ligands in several brain areas, expression of EphA4 in the suprachiasmatic nuclei of the hypothalamus (SCN), and finally an unchanged number of cells expressing Vip, Grp and Avp in the SCN of EphA4 KO mice. Conclusions: Our results suggest that EphA4 is involved in circadian sleep regulation.",
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AU - Freyburger, Marlène

AU - Pierre, Audrey

AU - Paquette, Gabrielle

AU - Bélanger-Nelson, Erika

AU - Bedont, Joseph

AU - Gaudreault, Pierre Olivier

AU - Drolet, Guy

AU - Laforest, Sylvie

AU - Blackshaw, Seth

AU - Cermakian, Nicolas

AU - Doucet, Guy

AU - Mongrain, Valérie

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N2 - Study Objectives: Optimal sleep is ensured by the interaction of circadian and homeostatic processes. Although synaptic plasticity seems to contribute to both processes, the specific players involved are not well understood. The EphA4 tyrosine kinase receptor is a cell adhesion protein regulating synaptic plasticity. We investigated the role of EphA4 in sleep regulation using electrocorticography in mice lacking EphA4 and gene expression measurements. Methods: EphA4 knockout (KO) mice, ClockΔ19/Δ19 mutant mice and littermates, C57BL/6J and CD-1 mice, and Sprague-Dawley rats were studied under a 12 h light: 12 h dark cycle, under undisturbed conditions or 6 h sleep deprivation (SLD), and submitted to a 48 h electrophysiological recording and/or brain sampling at different time of day. Results: EphA4 KO mice showed less rapid eye movement sleep (REMS), enhanced duration of individual bouts of wakefulness and nonrapid eye movement sleep (NREMS) during the light period, and a blunted daily rhythm of NREMS sigma activity. The NREMS delta activity response to SLD was unchanged in EphA4 KO mice. However, SLD increased EphA4 expression in the thalamic/hypothalamic region in C57BL/6J mice. We further show the presence of E-boxes in the promoter region of EphA4, a lower expression of EphA4 in Clock mutant mice, a rhythmic expression of EphA4 ligands in several brain areas, expression of EphA4 in the suprachiasmatic nuclei of the hypothalamus (SCN), and finally an unchanged number of cells expressing Vip, Grp and Avp in the SCN of EphA4 KO mice. Conclusions: Our results suggest that EphA4 is involved in circadian sleep regulation.

AB - Study Objectives: Optimal sleep is ensured by the interaction of circadian and homeostatic processes. Although synaptic plasticity seems to contribute to both processes, the specific players involved are not well understood. The EphA4 tyrosine kinase receptor is a cell adhesion protein regulating synaptic plasticity. We investigated the role of EphA4 in sleep regulation using electrocorticography in mice lacking EphA4 and gene expression measurements. Methods: EphA4 knockout (KO) mice, ClockΔ19/Δ19 mutant mice and littermates, C57BL/6J and CD-1 mice, and Sprague-Dawley rats were studied under a 12 h light: 12 h dark cycle, under undisturbed conditions or 6 h sleep deprivation (SLD), and submitted to a 48 h electrophysiological recording and/or brain sampling at different time of day. Results: EphA4 KO mice showed less rapid eye movement sleep (REMS), enhanced duration of individual bouts of wakefulness and nonrapid eye movement sleep (NREMS) during the light period, and a blunted daily rhythm of NREMS sigma activity. The NREMS delta activity response to SLD was unchanged in EphA4 KO mice. However, SLD increased EphA4 expression in the thalamic/hypothalamic region in C57BL/6J mice. We further show the presence of E-boxes in the promoter region of EphA4, a lower expression of EphA4 in Clock mutant mice, a rhythmic expression of EphA4 ligands in several brain areas, expression of EphA4 in the suprachiasmatic nuclei of the hypothalamus (SCN), and finally an unchanged number of cells expressing Vip, Grp and Avp in the SCN of EphA4 KO mice. Conclusions: Our results suggest that EphA4 is involved in circadian sleep regulation.

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KW - Sigma activity

KW - Suprachiasmatic nuclei

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