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The Journal of Neuroscience, December 1, 2002, 22(23):10427-10433
Loss of Photic Entrainment and Altered Free-Running Circadian
Rhythms in math5 / Mice
Raymond
Wee1,
Ana Maria
Castrucci3,
Ignacio
Provencio3,
Lin
Gan4, and
Russell N.
Van
Gelder1, 2
Departments of 1 Ophthalmology and Visual Sciences and
2 Molecular Biology and Pharmacology, Washington University
Medical School, St. Louis, Missouri 63110, 3 Department of
Anatomy, Physiology, and Genetics, Uniformed Services University of
Health Sciences, Bethesda, Maryland 20814, and 4 Department
of Neurobiology and Anatomy, University of Rochester Medical School,
Rochester, New York 14642
Mammalian free-running circadian rhythms are entrained to the
external light/dark cycle by photic signaling to the suprachiasmatic nuclei via the retinohypothalamic tract (RHT). We investigated the
circadian entrainment and clock properties of
math5 / mutant mice.
math5 is a critical regulator of retinal ganglion cell
development; math5/ mice show
severe optic nerve hypoplasia. By anterograde cholera toxin B tracing,
we find that math5/ mice do not
develop an identifiable RHT pathway. This appears to be attributable to
agenesis or dysgenesis of the majority of RHT-projecting retinal
ganglion cells. math5/ mice
display free-running circadian rhythms with a period ~1 hr longer
than B6/129 controls (24.43 ± 0.10 vs 23.62 ± 0.19 hr; p < 0.00001). The free-running period of
heterozygote mice is indistinguishable from that of controls.
math5/ mice show no entrainment
to light/dark cycles, whereas heterozygote mice show normal entrainment
to both 12 hr light/dark cycles and to a 1 hr skeletal photoperiod.
math5/ mice show reduced ability
to entrain their rhythms to the nonphotic time cue of restricted
running wheel access but demonstrate both free-running behavior and
entrained anticipation of wheel unlocking in these conditions,
suggesting the presence of a second diurnal oscillatory system in
math5/ animals. These results
demonstrate that retinal ganglion cell input is not necessary for the
development of a free-running circadian timekeeping system in the
suprachiasmatic nucleus but is important for both photic entrainment
and determination of the free-running period.
Key words:
circadian rhythm; math5; photic entrainment; retinohypothalamic tract; nonphotic entrainment; phase shifting
Copyright © 2002 Society for Neuroscience 0270-6474/02/222310427-07$05.00/0
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