Basu Priyoneel, Wensel Adrienne L, McKibbon Reid, Lefebvre Nicole, Antle Michael C
Department of Psychology, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada; Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
Department of Psychology, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada; Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
Neurosci Lett. 2016 May 16;621:22-27. doi: 10.1016/j.neulet.2016.04.012. Epub 2016 Apr 7.
The mammalian circadian clock in the suprachiasmatic nucleus (SCN) can be reset by the cholinergic agonist carbachol. In hamsters, intraSCN carbachol produces phase advances during the day. This phenomenon has previously been attributed to the muscarinic receptors, as carbachol-induced phase shifts are blocked by pretreatment with the muscarinic antagonist atropine. The SCN contains all five muscarinic receptors, leaving open the question as to which muscarinic receptors mediate these shifts. Here we test two selective muscarinic agonists, the M1/4 agonist McN-A-343 and the M2/3 agonist bethanechol, in addition to the non-selective cholinergic agonist carbachol. Consistent with previous reports, carbachol produced significant phase advances when injected to the SCN during the mid-subjective day. At the doses used here, McN-A-343, but not bethanechol, also produced significant phase shifts when injected to the SCN during the mid-subjective day. Phase shifts to McN-A-343 were as large as those produced by carbachol, suggesting that activation of the M1/4 receptors alone can fully account for the daytime phase advances produced by cholinergic agonists. Given acetylcholine's role in arousal, and the similarity between phase advances to carbachol/McN-A-343 and to exercise and arousal manipulations, it is possible that acetylcholine may contribute to non-photic resetting of the circadian clock.
视交叉上核（SCN）中的哺乳动物生物钟可被胆碱能激动剂卡巴胆碱重置。在仓鼠中，SCN内注射卡巴胆碱在白天会导致相位提前。此前这一现象被归因于毒蕈碱受体，因为卡巴胆碱诱导的相位变化可被毒蕈碱拮抗剂阿托品预处理所阻断。SCN包含所有五种毒蕈碱受体，这就留下了一个问题，即哪种毒蕈碱受体介导了这些变化。除了非选择性胆碱能激动剂卡巴胆碱外，我们在此测试了两种选择性毒蕈碱激动剂，M1/4激动剂 McN-A-343 和 M2/3激动剂氨甲酰甲胆碱。与之前的报道一致，在主观日中午向SCN注射卡巴胆碱时会产生显著的相位提前。在此处使用的剂量下，McN-A-343（而非氨甲酰甲胆碱）在主观日中午注射到SCN时也会产生显著的相位变化。McN-A-343引起的相位变化与卡巴胆碱产生的变化一样大，这表明仅激活M1/4受体就能完全解释胆碱能激动剂在白天引起的相位提前。鉴于乙酰胆碱在觉醒中的作用，以及卡巴胆碱/McN-A-343引起的相位提前与运动和觉醒操作引起的相位提前之间的相似性，乙酰胆碱有可能参与了生物钟的非光重置。
