Cholinergic Modulation of Neuronal Excitability in the Rat Suprachiasmatic Nucleus
Open Access
- 1 March 2010
- journal article
- Published by American Physiological Society in Journal of Neurophysiology
- Vol. 103 (3), 1397-1409
- https://doi.org/10.1152/jn.00877.2009
Abstract
The central cholinergic system regulates both the circadian clock and sleep-wake cycle and may participate in the feedback control of vigilance states on neural excitability in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigate the mechanisms for cholinergic modulation of SCN neuron excitability. Cell-attached recordings indicate that the nonspecific cholinergic agonist carbachol (CCh) inhibited 55% and excited 21% SCN neurons, leaving 24% nonresponsive. Similar response proportions were produced by two muscarinic receptor [muscarinic acetylcholine receptor (mAChR)] agonists, muscarine and McN-A-343 (M1/4 agonist), but not by two nicotinic receptor (nAChR) agonists, nicotine and choline (α7-nAChR agonist), which, however, produced similar response proportions. Whole cell and perforated-patch recordings indicate that CCh inhibition of firing was mediated by membrane hyperpolarization due to activation of background K+ currents, which were sensitive to submillimolar concentrations of Ba2+ and to millimolar concentrations of TEA. RT-PCR analysis demonstrated the presence of mRNA for M1 to M5 mAChRs in SCN. The CCh-induced hyperpolarization and activation of background K+ currents were blocked by M4 antagonists and to a lesser degree by M1 antagonists but were insensitive to the antagonists for M2 or M3, suggesting the involvement of M4 and M1 mAChRs in mediating CCh inhibition of firing. CCh enhancement of firing was mediated by membrane depolarization, as a result of postsynaptic inhibition of background K+ currents. The multiple actions of cholinergic modulation via multiple receptors and ion channels may allow acetylcholine to finely control SCN neuron excitability in different physiological settings.Keywords
This publication has 32 references indexed in Scilit:
- Acid‐sensing ion channels in neurones of the rat suprachiasmatic nucleusThe Journal of Physiology, 2009
- Two-State Models and the Analysis of the Allosteric Effect of Gallamine at the M2Muscarinic ReceptorJournal of Pharmacology and Experimental Therapeutics, 2008
- Serotonin Inhibits Neuronal Excitability by Activating Two-Pore Domain K+ Channels in the Entorhinal CortexPublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2007
- New light on an old paradox: site-dependent effects of carbachol on circadian rhythmsExperimental Neurology, 2005
- Sleep states alter activity of suprachiasmatic nucleus neuronsNature Neuroscience, 2003
- Muscarinic receptors mediate carbachol-induced phase shifts of circadian activity rhythms in Syrian hamstersBrain Research, 1996
- A toxin from the green mamba Dendroaspis angusticeps: Amino acid sequence and selectivity for muscarinic m4 receptorsFEBS Letters, 1994
- Localization of cholinergic neurons in the forebrain and brainstem that project to the suprachiasmatic nucleus of the hypothalamus in ratJournal of Comparative Neurology, 1993
- Phase-shifting mechanisms in the mammalian circadian system: new light on the carbachol paradoxJournal of Neuroscience, 1993
- Neurochemical basis for the photic control of circadian rhythms and seasonal reproductive cycles: role for acetylcholine.Proceedings of the National Academy of Sciences, 1985