SLEEP 2011 Abstract Supplement

A. Basic Science VI. Chronobiology
the remaining 10 subjects, the average phase shift was 40 +/- 15 minutes
(median 35 minutes; range 23 -67 minutes).
Conclusion: The human circadian system is more sensitive to short
duration LE that would be predicted by previous studies of the human
circadian phase-shifting response. This study is the first to demonstrate
a significant phase shift in humans to continuous LE durations of less
than 10 minutes.
Support (If Any): NIH RC2-HL101340-0 (EBK, SWL, SAR, REK),
NIH K02-HD045459 (EBK), NIH K24-HL105663 (EBK), T32-
HL07901 (MSH), NIH UL1 RR 025758
0155
THE ROLE OF THE SUPRACHIASMATIC NUCLEUS IN
MEDIATING THE NON-CIRCADIAN DIRECT EFFECTS OF
LIGHT ON SLEEP AND ALERTNESS
Hubbard J 1 , Ruppert E 1 , Tsai J 2 , Hannibal J 3 , Hagiwara G 2 , Colas D 2 ,
Franken P 4 , Bourgin PL 1
1
Neuroscience, University of Strasbourg, Strasbourg, France, 2 Biology,
Stanford University, Stanford, CA, USA, 3 Clinical Biochemistry,
Rigshopitalet, Copenhagen, Denmark, 4 University of Lausanne,
Lausanne, Switzerland
Introduction: Light can influence sleep and vigilance indirectly,
through a well-defined circadian pathway involving the suprachiasmatic
nucleus (SCN), or directly through non-visual, non-circadian effects.
This will determine the timing and quality of sleep and alertness through
an interaction with the circadian and homeostatic drives. Melanopsin
(Opn4), a retinal photopigment crucial for conveying non-visual light
information to brain areas, is a key mediator of this function. Recently,
our group confirmed that induction of c-Fos by light in the SCN was
lower in mice lacking melanopsin, linked to the reduced ability to phaseshift
the circadian rhythm. However, this does not rule out the possibility
of the SCN acting as a relay for these direct effects.
Methods: Wild-type and KO melanopsin mice were recorded for EEG
under 3 SCN conditions: intact, sham and “arrhythmic”, and the following
light-dark regimens: LD12h:12h, 1h L- or D-pulses during the 12h
D- or L-period, and a 24-hour period of LD1h:1h cycles. An anatomical
study of the SCN and retinohypothalamic tract was performed (triple
immunohistochemistry staining of the main SCN neurotransmitters,
AVP, VIP, and CTB- for tracing.)
Results: Mice with lesioned SCNs have a flattened sleep/wake rhythm
consistent with the removal of the circadian drive. Furthermore, after removal
of the SCN, the sleep-promoting effect of light and alerting effect
of darkness, evidenced under the 1h:1h LD ultradian cycle, are partly
abolished in both genotypes, similar to the intact Opn4-/- mice. Anatomical
analysis shows a complete lesion of the SCN sparing surrounding
brain structures. Staining of the retinohypothalamic fibers to the VLPO
and other areas, were conserved in lesioned animals.
Conclusion: Comprehensive analysis is ongoing to confirm these findings
which suggest that the SCN is one of several possible relays mediating
the direct effects of light on sleep and alertness and playing a role
beyond its function as circadian master clock.
0156
COMBINATION OF BRIGHT LIGHT AND EXOGENOUS
MELATONIN FOR PHASE ADVANCING THE HUMAN
CIRCADIAN CLOCK
Burke TM, Markwald RR, Chinoy ED, Snider JA, Bessman SC,
Jung CM, Wright KP
Integrative Physiology, Univeristy of Colorado at Boulder, Boulder,
CO, USA
Introduction: Photic and non-photic time cues have both been used
to phase shift the human circadian clock. The combination of light and
melatonin may be more efficient at phase shifting the circadian clock
than either treatment alone. Therefore, we examined the influence of
a single pulse of bright light exposure and a single administration of
exogenous melatonin alone and in combination in a protocol designed to
induce a phase advance shift of the human circadian clock.
Methods: 32 young healthy subjects [18 males (22.3±3.9yr;mean±SD)]
were studied in a 3.7 day in-laboratory phase shifting protocol. The effects
of four conditions (dim light-placebo, dim light-melatonin, bright
light-placebo, bright light-melatonin) on circadian phase measured by
salivary dim light melatonin onset (DLMO) were assessed prior to and
following treatment under constant routine conditions. Melatonin (5mg)
or placebo was administered 6h prior to habitual bedtime and 3h of
bright light (~3000 lux) exposure started 1h prior to habitual waketime.
Subjects were otherwise maintained in dim room light (