the suprachiasmatic nucleus (scn) a mammalian pacemaker
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The Suprachiasmatic Nucleus (SCN) A Mammalian Pacemaker. Joshua Gooley MCB 186: Circadian Biology October 19, 2005. The SCN is located in the anterior hypothalamus. Krieg, 1932. Location of the SCN in Human. Moore, 1991. The SCN receives direct retinal input. Hendrickson et al., 1972 - PowerPoint PPT PresentationTRANSCRIPT
The Suprachiasmatic Nucleus (SCN)
A Mammalian Pacemaker
Joshua Gooley
MCB 186: Circadian BiologyOctober 19, 2005
The SCN is located in the anterior hypothalamus
Krieg, 1932
Moore, 1991
Location of the SCN in Human
The SCN receives direct retinal input
Hendrickson et al., 1972Moore and Lenn, 1972
SCN Lesion
SCN lesions eliminate corticosteroid rhythm
Moore, 1972
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
SCN lesions block circadian rhythm of sleep
Ibuka et al., 1977
Solid line: Sham
Dashed line: SCN-X
DG
Nissl
0900 2100
The SCN is shows diurnal rhythm of glucose utilization
Lights on: 0600-1800
Schwartz and Gainer, 1977
Circadian rhythm of electrical activity persists in the SCN isolated in vivo – the “SCN island experiment”
Inouye and Kawamura, 1979
Circadian rhythms measured in hypothalamic slices
Martha Gillette
Multiunit electrical activity Vasopressin Release
The Tau hamster displays a short circadian period
Ralph and Menaker
Normal Heterozygous Homozygous mutant
Circadian period is genetically encoded in the SCN
Ralph et al., 1990
Welsh et al., 1995
Individual SCN neurons show circadian rhythm of electrical activity and display different periods
Dunlap, 1999
Light- and circadian-regulated expression of clock genes in the SCN
Antle and Silver, 2005
The SCN determines the circadian phase of behavior
de la Iglesia, 2000
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
Many genes are under circadian regulation in the SCN with broadly distributed circadian phases
Panda et al., 2002
The SCN is heterogeneously organized
Gooley and Saper, 2004 Karatsoreos et al., 2004
Antle and Silver, 2005
The SCN is functionally subdivided
VIP signaling is required for circadian expression of behavioral rhythms
Harmar et al., 2004
Inputs to the Suprachiasmatic Nucleus
Gooley and Saper, 2004
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)
Cassone et al., 1996
Circadian entrainment by exogenous melatonin
Melatonin binding in SCN
Weaver, 1991
Efferent projections of the Suprachiasmatic Nucleus
Gooley and Saper, 2004
Circadian outflow pathways from the SCN
Saper et al., 2005
Polymer-encapsulatedSCN graft
Diffusible factors can regulate behavioral rhythms
Silver et al., 1996
EGF receptor signaling can regulate behavior
Kramer et al., 2001
Prokineticin 2 inhibits behavioral activity
Cheng et al., 2002
saline PK2
…but it is not the only circadian clock
BehaviorPhysiology
The SCN is a light entrainable circadian clock…