1. The Suprachiasmatic Nucleus (SCN)
A Mammalian Pacemaker
Joshua Gooley
MCB 186: Circadian Biology
October 19, 2005

2. The SCN is located in the anterior hypothalamus
Krieg, 1932

3. Location of the SCN in Human
Moore, 1991

4. The SCN receives direct retinal input
Hendrickson et al., 1972
Moore and Lenn, 1972

5. SCN lesions eliminate corticosteroid rhythm
Moore, 1972

6. SCN lesions disrupt circadian rhythms
Drinking Rhythm
Enucleated
SCN-X 12 24 12 24
Body Temperature
Locomotor Activity
Sham
SCN-X
Sham
SCN-X
Stephan and Zucker, 1972; Kittrell, 1988

7. SCN lesions block circadian rhythm of sleep
Solid line: Sham
Dashed line: SCN-X
Ibuka et al., 1977

8. The SCN is shows diurnal rhythm of glucose utilization
0900
2100 DG
Nissl
Lights on:
Schwartz and Gainer, 1977

9. Circadian rhythm of electrical activity persists in the SCN isolated in vivo – the “SCN island experiment”
Inouye and Kawamura, 1979

10. Circadian rhythms measured in hypothalamic slices
Martha Gillette
Multiunit electrical activity
Vasopressin Release

11. The Tau hamster displays a short circadian period
Normal
Heterozygous
Homozygous mutant
Ralph and Menaker

12. Circadian period is genetically encoded in the SCN
Ralph et al., 1990

13. Individual SCN neurons show circadian rhythm of electrical activity and display different periods
Welsh et al., 1995

14. Light- and circadian-regulated expression of clock genes in the SCN
Antle and Silver, 2005
Dunlap, 1999

15. The SCN determines the circadian phase of behavior
de la Iglesia, 2000

16. Individual SCN neurons show circadian expression of Per1 in hypothalamic slices
Per1-luciferase rhythm in individual SCN neurons
Circadian rhythm of Per1
In four SCN neurons
Wild Type: Per1 circadian
rhythm is robust in individual
SCN neurons
Double Cry knockout:
Per1 rhythm is lost in
individual SCN neurons
Yamaguchi et al., 2003

17. Many genes are under circadian regulation in the SCN with broadly distributed circadian phases
Panda et al., 2002

18. The SCN is heterogeneously organized
Gooley and Saper, 2004
Karatsoreos et al., 2004

19. The SCN is functionally subdivided
Antle and Silver, 2005

20. VIP signaling is required for circadian expression of behavioral rhythms
Harmar et al., 2004

21. Inputs to the Suprachiasmatic Nucleus
Gooley and Saper, 2004

22. The intergeniculate leaflet and median raphe nucleus project to the suprachiasmatic nucleus
IGL (retros from SCN)
MRN (5-HT)
MRN (retros from SCN)
Morin et al., 2004; Leander et al., 1998

23. Circadian entrainment by exogenous melatonin
Melatonin binding in SCN
Weaver, 1991
Cassone et al., 1996

24. Efferent projections of the Suprachiasmatic Nucleus
Gooley and Saper, 2004

25. Circadian outflow pathways from the SCN
Saper et al., 2005

26. Diffusible factors can regulate behavioral rhythms
Polymer-encapsulated
SCN graft
Silver et al., 1996

27. EGF receptor signaling can regulate behavior
Kramer et al., 2001

28. Prokineticin 2 inhibits behavioral activity
saline
PK2
Cheng et al., 2002

29. The SCN is a light entrainable circadian clock…
Behavior
Physiology
…but it is not the only circadian clock