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Journal of Neuroscience, Vol 16, 744-751, Copyright © 1996 by Society for Neuroscience
Cholinergic regulation of the suprachiasmatic nucleus circadian rhythm via a muscarinic mechanism at night
C Liu and MU Gillette
Neuroscience Program, University of Illinois at Urbana-Champaign 61801, USA.
In mammals, the suprachiasmatic nucleus (SCN) is responsible for the
generation of most circadian rhythms and for their entrainment to
environmental cues. Carbachol, an agonist of acetylcholine (ACh), has been
shown to shift the phase of circadian rhythms in rodents when injected
intracerebroventricularly. However, the site and receptor type mediating
this action have been unknown. In the present experiments, we used the
hypothalamic brain-slice technique to study the regulation of the SCN
circadian rhythm of neuronal firing rate by cholinergic agonists and to
identify the receptor subtypes involved. We found that the phase of the
oscillation in SCN neuronal activity was reset by a 5 min treatment with a
carbachol microdrop (1 microliter, 100 microM), but only when applied
during the subjective night, with the largest phase shift (+ 6 hr) elicited
during the middle of the subjective night. This effect also was produced by
ACh and two muscarinic receptor (mAChR) agonists, muscarine and McN-A-343
(M1-selective), but not by nicotine. Furthermore, the effect of carbachol
was blocked by the mAChR antagonist atropine (0.1 microM), not by two
nicotinic antagonists, dihydro-beta-erythroidine (10 microM) and
d-tubocurarine (10 microM). The M1-selective mAChR antagonist pirenzepine
completely blocked the carbachol effect at 1 microM, whereas an
M3-selective antagonist, 4,2- (4,4'-diacetoxydiphenylmethyl)pyridine,
partially blocked the effect at the same concentration. These results
demonstrate that carbachol acts directly on the SCN to reset the phase of
its firing rhythm during the subjective night via an M1-like mAChR.
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