Ebling F J
Department of Anatomy, University of Cambridge, U.K.
Prog Neurobiol. 1996 Oct;50(2-3):109-32. doi: 10.1016/s0301-0082(96)00032-9.
Endogenous circadian rhythms govern most aspects of physiology and behaviour in mammals, including body temperature, autonomic and endocrine function, and sleep-wake cycles. Such rhythms are generated by the suprachiasmatic nucleus of the hypothalamus (SCN), but are synchronised to the environmental light-dark cycle by photic cues perceived by the retina and conveyed to the SCN via the retinohypothalamic tract (RHT). This review considers many lines of evidence from diverse experimental approaches indicating that the RHT employs glutamate (or a related excitatory amino acid) as a neurotransmitter. Ultrastructural studies demonstrate the presence of glutamate in presynaptic terminals within the SCN. In situ hybridisation and immunocytochemical studies reveal the presence of several NMDA (NMDAR1, NMDAR2C), non-NMDA (GluR1, GluR2, GluR4) and metabotropic (mGluR1) glutamate receptor subunits in the SCN. Messenger RNA encoding a glutamate transporter protein is also present. In behavioural tests, glutamate antagonists can block the effects of light in phase-shifting circadian rhythms. Such treatments also block the induction of c-fos within SCN cells by light, whereas a glutamate agonist (NMDA) induces c-fos expression. In hypothalamic slice preparations in vitro, electrical stimulation of the optic nerves induces release of glutamate and aspartate, and glutamate antagonists block field potentials in the SCN evoked by stimulation of the optic nerve. Circadian rhythms of electrical activity which persist in vitro are phase shifted by application of glutamate in a manner which mimics the phase shifting effects of light in vivo. This wide range of experimental findings provides strong support for the hypothesis that glutamate is the principal neurotransmitter within the RHT, and thus conveys photic cues to the circadian timing system in the SCN.
内源性昼夜节律控制着哺乳动物生理和行为的大多数方面，包括体温、自主神经和内分泌功能以及睡眠-觉醒周期。这种节律由下丘脑视交叉上核（SCN）产生，但通过视网膜感知的光信号并经视网膜下丘脑束（RHT）传递至SCN，从而与环境明暗周期同步。本综述考虑了来自各种实验方法的多条证据，表明RHT使用谷氨酸（或一种相关的兴奋性氨基酸）作为神经递质。超微结构研究证明SCN内突触前终末存在谷氨酸。原位杂交和免疫细胞化学研究揭示SCN中存在几种NMDA（NMDAR1、NMDAR2C）、非NMDA（GluR1、GluR2、GluR4）和代谢型（mGluR1）谷氨酸受体亚单位。也存在编码谷氨酸转运蛋白的信使核糖核酸。在行为测试中，谷氨酸拮抗剂可阻断光对昼夜节律相位移动的影响。此类处理还可阻断光诱导SCN细胞内c-fos的表达，而谷氨酸激动剂（NMDA）可诱导c-fos表达。在体外下丘脑脑片制备中，对视神经的电刺激可诱导谷氨酸和天冬氨酸的释放，谷氨酸拮抗剂可阻断视神经刺激在SCN中诱发的场电位。体外持续存在的电活动昼夜节律可通过应用谷氨酸而发生相位移动，其方式类似于体内光的相位移动效应。这一系列广泛的实验结果为谷氨酸是RHT内主要神经递质这一假说提供了有力支持，因此谷氨酸将光信号传递至SCN中的昼夜节律计时系统。
