Malek Z S, Pévet P, Raison S
Laboratoire de Neurobiologie des Rythmes UMR 7518 CNRS/ULP, IFR Neurosciences, Université Louis Pasteur, 12, rue de l'Université 67000 Strasbourg, France.
Neuroscience. 2004;125(3):749-58. doi: 10.1016/j.neuroscience.2004.01.031.
Serotonin (5-HT) is involved in the synchronisation of the mammalian circadian clock located in the suprachiasmatic nuclei of the hypothalamus (SCN). This clock is synchronised by light (photic cues) and by non-photic cues. Non-photic cues are notably conveyed to the SCN by a direct 5-HT pathway arising from the mesencephalic median raphe nucleus (MRN). Furthermore, an indirect projection conveys non-photic inputs by 5-HT fibres from the mesencephalic dorsal raphe nucleus (DRN) to the intergeniculate leaflets of the thalamus (IGL) which project to the SCN. In the rat, the quantitative distribution of tryptophan hydroxylase (TpH), used as an index of 5-HT synthesis, was studied by in situ immunoautoradiography in both the serotoninergic cell bodies area of the raphe nuclei and the serotoninergic terminal field of the IGL. Under a 12 h light: 12 h dark (LD 12:12), TpH protein amount exhibited a rhythmic variation within the IGL. The maximum levels were reached at the day/night transition. In both MRN and the lateral groups of the DRN, TpH variations were opposite to those observed in the IGL. Such phase opposition was reported previously in the MRN/SCN pathway and was correlated with a rhythmic release of 5-HT within the SCN [Eur J Neurosci 15 (2002) 833]. Thus, the daily rhythmicity of TpH levels observed in DRN-IGL pathway may be correlated with a rhythmic release of 5-HT in the IGL at the beginning of the night. Under constant darkness, TpH rhythmic variations in the two serotoninergic pathways were maintained and similar to those observed under light/dark cycle. These results demonstrate the existence of a circadian endogenous functioning in the 5-HT neurones projecting to the rat circadian system.
血清素（5-羟色胺，5-HT）参与位于下丘脑视交叉上核（SCN）的哺乳动物生物钟的同步调节。该生物钟通过光（光信号）和非光信号进行同步。非光信号尤其通过中脑正中缝核（MRN）产生的直接5-HT通路传递至SCN。此外，一条间接投射通路通过5-HT纤维将非光信号从中脑背侧缝核（DRN）传递至丘脑膝间小叶（IGL），后者再投射至SCN。在大鼠中，通过原位免疫放射自显影技术，研究了作为5-HT合成指标的色氨酸羟化酶（TpH）在缝核5-羟色胺能细胞体区域和IGL的5-羟色胺能终末场中的定量分布。在12小时光照：12小时黑暗（LD 12:12）条件下，TpH蛋白量在IGL内呈现节律性变化。在白天/黑夜转换时达到最高水平。在MRN和DRN的外侧组中，TpH的变化与在IGL中观察到的相反。这种相位相反现象先前在MRN/SCN通路中已有报道，并且与SCN内5-HT的节律性释放相关[《欧洲神经科学杂志》15（2002）833]。因此，在DRN-IGL通路中观察到的TpH水平的每日节律性可能与夜间开始时IGL中5-HT的节律性释放相关。在持续黑暗条件下，两条5-羟色胺能通路中TpH的节律性变化得以维持，且与在光/暗循环条件下观察到的相似。这些结果证明了投射至大鼠昼夜节律系统的5-羟色胺能神经元中存在昼夜内源性功能。
