TY - JOUR
T1 - Cholinergic regulation of the suprachiasmatic nucleus circadian rhythm via a muscarinic mechanism at night
AU - Liu, Chen
AU - Gillette, Martha U.
PY - 1996/1/15
Y1 - 1996/1/15
N2 - 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 μl, 100 μM), 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 μM), not by two nicotinic antagonists, dihydro-β-erythroidine (10 μM) and d-tubocurarine (10 μM). The M1- selective mAChR antagonist pirenzepine completely blocked the carbachol effect at 1 μM, 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 SON to reset the phase of its firing rhythm during the subjective night via an M1-like mAChR.
AB - 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 μl, 100 μM), 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 μM), not by two nicotinic antagonists, dihydro-β-erythroidine (10 μM) and d-tubocurarine (10 μM). The M1- selective mAChR antagonist pirenzepine completely blocked the carbachol effect at 1 μM, 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 SON to reset the phase of its firing rhythm during the subjective night via an M1-like mAChR.
KW - 4-DAMP
KW - acetylcholine
KW - atropine
KW - carbachol
KW - circadian rhythm
KW - d-tubocurarine
KW - dihydro-β- erythroidine
KW - McN-A-343
KW - muscarinic receptor
KW - nicotine
KW - pirenzepine
KW - suprachiasmatic nucleus
UR - http://www.scopus.com/inward/record.url?scp=0030030035&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030030035&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.16-02-00744.1996
DO - 10.1523/jneurosci.16-02-00744.1996
M3 - Article
C2 - 8551357
AN - SCOPUS:0030030035
VL - 16
SP - 744
EP - 751
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 2
ER -