C. Liu et Mu. Gillette, CHOLINERGIC REGULATION OF THE SUPRACHIASMATIC NUCLEUS CIRCADIAN-RHYTHM VIA A MUSCARINIC MECHANISM AT NIGHT, The Journal of neuroscience, 16(2), 1996, pp. 744-751
In mammals, the suprachiasmatic nucleus (SCN) is responsible for the g
eneration of most circadian rhythms and for their entrainment to envir
onmental 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 mediat
ing 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 phas
e of the oscillation in SCN neuronal activity was reset by a 5 min tre
atment with a carbachol microdrop (1 mu l, 100 mu M), but only when ap
plied 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, mus
carine and McN-A-343 (M1-selective), but not by nicotine. Furthermore,
the effect of carbachol was blocked by the mAChR antagonist atropine
(0.1 mu M), not by two nicotinic antagonists, dihydro-beta-erythroidin
e (10 mu M) and d-tubocurarine (10 mu M). The M1-selective mAChR antag
onist pirenzepine completely blocked the carbachol effect at 1 mu M, w
hereas an M3-selective antagonist, 4,2-(4,4'-diacetoxydiphenylmethyl)p
yridine, 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-l
ike mAChR.