Kalsbeek A, Cutrera R A, Van Heerikhuize J J, Van Der Vliet J, Buijs R M
Netherlands Institute for Brain Research, Amsterdam.
Neuroscience. 1999;91(2):453-61. doi: 10.1016/s0306-4522(98)00635-6.
The daily rhythm of melatonin production in the mammalian pineal is driven by the endogenous circadian pacemaker in the suprachiasmatic nuclei. The major release period of melatonin is closely linked to the dark phase of the 24-h day/night cycle. Environmental light will affect melatonin release in two ways: (i) it entrains the rhythm of the circadian oscillator; and (ii) it causes an acute suppression of nocturnal melatonin release. These two effects of light are both mediated by the suprachiasmatic nucleus and enable the pineal gland to convey information about day length to the reproductive system through changes in melatonin levels. Glutamate is currently believed to be the major transmitter in the retinal ganglion cell fibers reaching the suprachiasmatic nucleus. At present no information is available, however, about the transmitter(s) implicated in the further propagation, i.e. from the suprachiasmatic nucleus onwards, of the light information. In the present study we provide evidence that the endogenous release of GABA from suprachiasmatic nucleus terminals is implicated in the further transmission of light information to the pineal gland. Bilateral administration of the GABA-antagonist bicuculline to hypothalamic target areas of the suprachiasmatic nucleus completely prevents the inhibitory effect of nocturnal light on melatonin secretion and the present study thus documents that retina-mediated photic activation of suprachiasmatic nucleus neurons induces the release of GABA from efferent suprachiasmatic nucleus nerve terminals, resulting in an inhibition of melatonin release by the pineal gland. Together with our previous (electro)physiological data these results identify GABA as an important mediator of rapid synaptic transmission of suprachiasmatic nucleus output to its target areas.
哺乳动物松果体中褪黑素分泌的日常节律由视交叉上核中的内源性昼夜节律起搏器驱动。褪黑素的主要释放期与24小时昼夜周期的黑暗阶段密切相关。环境光会通过两种方式影响褪黑素的释放：（i）它调节昼夜节律振荡器的节律；（ii）它会导致夜间褪黑素释放的急性抑制。光的这两种作用均由视交叉上核介导，并使松果体能够通过褪黑素水平的变化将有关白昼长度的信息传递给生殖系统。目前认为谷氨酸是到达视交叉上核的视网膜神经节细胞纤维中的主要神经递质。然而，目前尚无关于光信息进一步传播（即从视交叉上核开始）所涉及的神经递质的信息。在本研究中，我们提供证据表明，视交叉上核终末内源性释放的γ-氨基丁酸（GABA）与光信息向松果体的进一步传递有关。向视交叉上核的下丘脑靶区域双侧注射GABA拮抗剂荷包牡丹碱，可完全阻止夜间光照对褪黑素分泌的抑制作用，因此本研究证明，视网膜介导的视交叉上核神经元的光激活会诱导GABA从视交叉上核传出神经终末释放，从而导致松果体对褪黑素释放的抑制。这些结果与我们之前的（电）生理数据一起，确定GABA是视交叉上核输出向其靶区域快速突触传递的重要介质。
