title: Anterior Insula Regulates Multiscale Temporal Organization of Sleep and Wake Activity.
abstract: The role of specific cortical regions in sleep-regulating circuits is unclear. The anterior insula (AI) has strong reciprocal connectivity with wake and sleep-promoting hypothalamic and brainstem regions, and we hypothesized that the AI regulates patterns of sleep and wakefulness. To test this hypothesis, we lesioned the AI in rats (n = 8) and compared sleep, wake, and activity regulation in these animals with nonlesioned controls (n = 8) with 24-h sleep recordings and chronic infrared activity monitoring. Compared to controls, animals with AI lesions had decreased wakefulness and increased rapid eye movement (REM) sleep and non-REM (NREM) sleep. AI-lesioned animals had shorter wake bouts, especially during the active dark phase. AI-lesioned animals also had more transitions from NREM to REM sleep, especially during the inactive light phase. Chronic infrared monitoring revealed that AI-lesioned animals also had a disturbed temporal organization of locomotor activity at multiple time scales with more random activity fluctuations from 4 to 12 h despite intact circadian rhythms. These results suggest that the AI regulates sleep and activity and contributes to the regulation of sleep and motor behavior rhythmicity across multiple time scales. Dysfunction of the AI may underlie changes in sleep-wake patterns in neurological diseases.
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Division of Sleep Medicine, Boston, MA mcchen@alumni.stanford.edu.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Departments of Neurology and Medicine, Division of Sleep and Circadian Disorders, Boston, MA.
authors.forename: Wei-Yin
authors.initials: WY
authors.lastname: Chiang
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Departments of Neurology and Medicine, Division of Sleep and Circadian Disorders, Boston, MA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Yugay
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Departments of Neurology and Medicine, Division of Sleep and Circadian Disorders, Boston, MA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Patxot
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Division of Sleep Medicine, Boston, MA.
authors.forename: İpek Betül
authors.initials: İB
authors.lastname: Özçivit
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Departments of Neurology and Medicine, Division of Sleep and Circadian Disorders, Boston, MA.
authors.forename: Kun
authors.initials: K
authors.lastname: Hu
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Division of Sleep Medicine, Boston, MA.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000502:physiology* / Q000601:surgery; D002940:Circadian Rhythm / Q000502:physiology*; D004569:Electroencephalography; D008027:Light; D008124:Locomotion; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology; D051381:Rats; D012890:Sleep; D012895:Sleep, REM; D014851:Wakefulness
keywords: NREM sleep; REM sleep; activity; insula; multiscale; sleep; wake
references.citation: Nat Rev Neurol. 2014 Feb;10(2):115-9
references.pmid: 24366271
references.citation: Nature. 2006 Jun 1;441(7093):589-94
references.pmid: 16688184
references.citation: Science. 1996 Jan 12;271(5246):216-9
references.pmid: 8539624
references.citation: J Comp Neurol. 1987 Aug 1;262(1):27-45
references.pmid: 2442207
references.citation: J Neurosci. 1981 Aug;1(8):876-86
references.pmid: 7346592
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13164-9
references.pmid: 17670944
references.citation: Annu Rev Neurosci. 2002;25:433-69
references.pmid: 12052916
references.citation: J Neurosci. 2000 May 15;20(10):3830-42
references.pmid: 10804223
references.citation: J Neurophysiol. 1980 Sep;44(3):440-55
references.pmid: 7441309
references.citation: J Neurosci. 2012 Dec 12;32(50):17970-6
references.pmid: 23238713
references.citation: PLoS One. 2012;7(11):e48927
references.pmid: 23185285
references.citation: J Comp Neurol. 2011 Apr 1;519(5):933-56
references.pmid: 21280045
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10227-32
references.pmid: 18645184
references.citation: Sci Rep. 2013;3:2229
references.pmid: 23863985
references.citation: J Comp Neurol. 1991 Jan 15;303(3):355-74
references.pmid: 2007654
references.citation: Nature. 2007 Nov 15;450(7168):420-4
references.pmid: 17943086
references.citation: J Nerv Ment Dis. 1999 Dec;187(12):707-12
references.pmid: 10665464
references.citation: Neuroscience. 2007 Nov 9;149(3):508-17
references.pmid: 17920204
references.citation: Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2320-4
references.pmid: 25675516
references.citation: J Neurosci. 2010 Oct 27;30(43):14543-51
references.pmid: 20980612
references.citation: J Comp Neurol. 1982 Sep 10;210(2):163-73
references.pmid: 7130477
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1608-13
references.pmid: 19164756
references.citation: Prog Brain Res. 1991;88:521-32
references.pmid: 1813932
references.citation: Exp Neurol. 1976 Oct;53(1):31-50
references.pmid: 183969
references.citation: Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20272-7
references.pmid: 24191004
references.citation: Neuropharmacology. 2014 Nov;86:125-32
references.pmid: 25036609
references.citation: Auton Neurosci. 2006 Apr 30;125(1-2):16-21
references.pmid: 16516558
references.citation: J Comp Neurol. 1998 Oct 5;399(4):440-68
references.pmid: 9741477
references.citation: Brain Res. 1986 Aug 6;379(2):329-41
references.pmid: 3742225
references.citation: J Sleep Res. 2004 Sep;13(3):179-208
references.pmid: 15339255
references.citation: Nat Neurosci. 2014 Sep;17(9):1217-24
references.pmid: 25129078
references.citation: J R Soc Interface. 2014 Jul 6;11(96). pii: 20140318. doi: 10.1098/rsif.2014.0318
references.pmid: 24829282
references.citation: Biol Psychol. 2014 Mar;97:1-8
references.pmid: 24412227
references.citation: Physica A. 2004 Jun;337(1-2):307-18
references.pmid: 15759365
references.citation: Neurosci Lett. 2000 May 19;285(3):231-3
references.pmid: 10806328
references.citation: Brain. 1997 Jul;120 ( Pt 7):1173-97
references.pmid: 9236630
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2490-4
references.pmid: 19202078
references.citation: Neuron. 2010 Dec 22;68(6):1023-42
references.pmid: 21172606
references.citation: Front Neurol. 2012 Jun 28;3:105
references.pmid: 23060850
references.citation: Biol Rev Camb Philos Soc. 2013 Nov;88(4):873-94
references.pmid: 23573942
references.citation: Nat Neurosci. 2010 Dec;13(12):1526-33
references.pmid: 21037585
references.citation: J Comp Neurol. 1991 Sep 1;311(1):1-16
references.pmid: 1719041