the suprachiasmatic nucleus (scn) a mammalian pacemaker joshua gooley mcb 186: circadian biology...
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The Suprachiasmatic Nucleus (SCN)
A Mammalian Pacemaker
Joshua Gooley
MCB 186: Circadian BiologyOctober 19, 2005
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The SCN is located in the anterior hypothalamus
Krieg, 1932
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Moore, 1991
Location of the SCN in Human
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The SCN receives direct retinal input
Hendrickson et al., 1972Moore and Lenn, 1972
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SCN Lesion
SCN lesions eliminate corticosteroid rhythm
Moore, 1972
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SCN-XShamBody Temperature
SCN-XShamLocomotor Activity
SCN lesions disrupt circadian rhythms
Stephan and Zucker, 1972; Kittrell, 1988
Drinking Rhythm
0 12 24 0 12 24
Enucleated SCN-X
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SCN lesions block circadian rhythm of sleep
Ibuka et al., 1977
Solid line: Sham
Dashed line: SCN-X
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DG
Nissl
0900 2100
The SCN is shows diurnal rhythm of glucose utilization
Lights on: 0600-1800
Schwartz and Gainer, 1977
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Circadian rhythm of electrical activity persists in the SCN isolated in vivo – the “SCN island experiment”
Inouye and Kawamura, 1979
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Circadian rhythms measured in hypothalamic slices
Martha Gillette
Multiunit electrical activity Vasopressin Release
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The Tau hamster displays a short circadian period
Ralph and Menaker
Normal Heterozygous Homozygous mutant
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Circadian period is genetically encoded in the SCN
Ralph et al., 1990
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Welsh et al., 1995
Individual SCN neurons show circadian rhythm of electrical activity and display different periods
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Dunlap, 1999
Light- and circadian-regulated expression of clock genes in the SCN
Antle and Silver, 2005
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The SCN determines the circadian phase of behavior
de la Iglesia, 2000
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Circadian rhythm of Per1In four SCN neurons
Wild Type: Per1 circadianrhythm is robust in individualSCN neurons
Per1-luciferase rhythm in individual SCN neurons
Double Cry knockout: Per1 rhythm is lost inindividual SCN neurons
Individual SCN neurons show circadian expression of Per1 in hypothalamic slices
Yamaguchi et al., 2003
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Many genes are under circadian regulation in the SCN with broadly distributed circadian phases
Panda et al., 2002
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The SCN is heterogeneously organized
Gooley and Saper, 2004 Karatsoreos et al., 2004
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Antle and Silver, 2005
The SCN is functionally subdivided
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VIP signaling is required for circadian expression of behavioral rhythms
Harmar et al., 2004
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Inputs to the Suprachiasmatic Nucleus
Gooley and Saper, 2004
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Morin et al., 2004; Leander et al., 1998
The intergeniculate leaflet and median raphe nucleus project to the suprachiasmatic nucleus
IGL (retros from SCN) MRN (5-HT) MRN (retros from SCN)
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Cassone et al., 1996
Circadian entrainment by exogenous melatonin
Melatonin binding in SCN
Weaver, 1991
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Efferent projections of the Suprachiasmatic Nucleus
Gooley and Saper, 2004
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Circadian outflow pathways from the SCN
Saper et al., 2005
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Polymer-encapsulatedSCN graft
Diffusible factors can regulate behavioral rhythms
Silver et al., 1996
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EGF receptor signaling can regulate behavior
Kramer et al., 2001
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Prokineticin 2 inhibits behavioral activity
Cheng et al., 2002
saline PK2
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…but it is not the only circadian clock
BehaviorPhysiology
The SCN is a light entrainable circadian clock…