title: Global Functional Connectivity Differences between Sleep-Like States in Urethane Anesthetized Rats Measured by fMRI.
abstract: Sleep is essential for nervous system functioning and sleep disorders are associated with several neurodegenerative diseases. However, the macroscale connectivity changes in brain networking during different sleep states are poorly understood. One of the hindering factors is the difficulty to combine functional connectivity investigation methods with spontaneously sleeping animals, which prevents the use of numerous preclinical animal models. Recent studies, however, have implicated that urethane anesthesia can uniquely induce different sleep-like brain states, resembling rapid eye movement (REM) and non-REM (NREM) sleep, in rodents. Therefore, the aim of this study was to assess changes in global connectivity and topology between sleep-like states in urethane anesthetized rats, using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging. We detected significant changes in corticocortical (increased in NREM-like state) and corticothalamic connectivity (increased in REM-like state). Additionally, in graph analysis the modularity, the measure of functional integration in the brain, was higher in NREM-like state than in REM-like state, indicating a decrease in arousal level, as in normal sleep. The fMRI findings were supported by the supplementary electrophysiological measurements. Taken together, our results show that macroscale functional connectivity changes between sleep states can be detected robustly with resting-state fMRI in urethane anesthetized rats. Our findings pave the way for studies in animal models of neurodegenerative diseases where sleep abnormalities are often one of the first markers for the disorder development.
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland.|Department of Control and Applied Mathematics, Moscow Institute of Physics and Technology, Moscow, Russia.
authors.forename: Ekaterina
authors.identifier: 0000-0003-2365-865X
authors.initials: E
authors.lastname: Zhurakovskaya
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Paasonen
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Artem
authors.initials: A
authors.lastname: Shatillo
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Lipponen
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Raimo
authors.initials: R
authors.lastname: Salo
authors.affiliation: Department of Control and Applied Mathematics, Moscow Institute of Physics and Technology, Moscow, Russia.|Institute of Theoretical and Experimental Biophysics, Puschino, Moscow Region, Russia.|Federal Scientific & Clinical Center for Federal Biomedical Agency of Russia, Moscow, Russia.
authors.forename: Rubin
authors.initials: R
authors.lastname: Aliev
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Gröhn
mesh_terms: D018686:Anesthetics, Intravenous; D000818:Animals; D001143:Arousal / Q000502:physiology; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000502:physiology*; D004569:Electroencephalography; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000033:anatomy & histology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012895:Sleep, REM / Q000502:physiology*; D013788:Thalamus / Q000033:anatomy & histology / Q000502:physiology*; D014520:Urethane; D014851:Wakefulness / Q000502:physiology
chemical_list: D018686:Anesthetics, Intravenous; D014520:Urethane