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Volume 17, Number 20,
Issue of October 15, 1997
pp. 7974-7987
Copyright ©1997 Society for Neuroscience
Both Neuropeptide Y and Serotonin Are Necessary for
Entrainment of Circadian Rhythms in Mice by Daily Treadmill Running
Schedules
Received May 8, 1997; revised July 25, 1997; accepted July 29, 1997.
Elliott G. Marchant,
Neil V. Watson, and
Ralph E. Mistlberger
Department of Psychology, Simon Fraser University, Burnaby, British
Columbia V5A 1S6, Canada
This study investigated the role of the suprachiasmatic nucleus
(SCN) circadian pacemaker and its neuropeptide Y (NPY) and serotonin
(5-HT) afferents in entrainment (synchronization) of mouse circadian
rhythms by treadmill running. Blind C57BL/6j mice were run in
treadmills for 3 hr/d for 3-10 weeks after receiving radio-frequency
lesions of the SCN or the intergeniculate leaflet (IGL, the source of
SCN NPY) or infusions of the 5-HT neurotoxin 5,7-DHT into the SCN area.
Of 25 intact mice, 22 entrained and three showed period ( , the mean
duration of the circadian cycle) modulations to scheduled running.
Arrhythmic SCN-ablated mice did not synchronize to scheduled running in
a way suggestive of circadian pacemaker mediation. Of 15 mice with IGL
lesions, only two with partial lesions entrained. Mice with complete
IGL lesions (five), confirmed by immunocytochemistry, showed no
entrainment or changes. Of 19 mice with 5-HT lesions, only two with
partial lesions entrained. All but two mice with complete (10) or
nearly complete (4) 5-HT denervation, confirmed by immunocytochemistry, showed modulations during the treadmill schedule. Failure to entrain was not explained by group differences in before the treadmill schedules. The results indicate that the SCN and both NPY and
5-HT are necessary for entrainment to 24 hr schedules of forced running
but that complete loss of 5-HT does not prevent modulations of
pacemaker motion by behavioral stimuli. Treadmill entrainment in mice
may involve synergistic interactions between 5-HT and NPY afferents at
some site within the circadian system.
Key words:
circadian rhythms;
entrainment;
neuropeptide Y;
serotonin;
intergeniculate leaflet;
raphe nuclei;
suprachiasmatic
nucleus;
treadmill running
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