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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 (tau , 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 tau  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 tau  modulations during the treadmill schedule. Failure to entrain was not explained by group differences in tau  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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