Sollars Patricia J, Ogilvie Malcolm D, Rea Michael A, Pickard Gary E
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523-1670, USA.
J Biol Rhythms. 2002 Oct;17(5):428-37. doi: 10.1177/074873002237137.
Serotonin (5-HT) can act presynaptically at 5-HT1B receptors on retinal terminals in the suprachiasmatic nucleus (SCN) to inhibit glutamate release, thereby modulating the effects of light on circadian behavior. 5-HT1B receptor agonists (1) inhibit light-induced phase shifts of circadian activity rhythms, (2) attenuate light-induced Fos expression in the SCN, and (3) reduce the amplitude of optic nerve-evoked excitatory postsynaptic currents in SCN neurons in vitro. To determine whether functional disruption of the 5-HT1B presynaptic receptors would result in an amplified response of the SCN to light, the period (tau) of the circadian rhythm of wheel-running activity was estimated under several different conditions in 5-HT1B receptor knockout (KO) mice and genetically matched wild-type animals. Under constant light (LL) conditions, the tau of 5-HT1B receptor KO mice was significantly greater than the tau of wild-type mice. A quantitative analysis of the wheel-running activity revealed no differences between wild-type and KO mice in either total activity or the temporal distribution of activity under LL conditions, suggesting that the observed increase in tau was not a function of reduced activity. Under constant dark conditions, the period of the circadian rhythm of wheel-running activity of wild-type and 5-HT1B receptor KO mice was similar. In addition, no differences were noted between wild-type and 5-HT1B receptor KO mice in the rate of reentrainment to a 6 h phase advance in the 12:12 light:dark cycle or in phase shifts in response to a 10 min light pulse presented at circadian time 16. The enhanced response of the SCN circadian clock of the 5-HT1B receptor KO mice to LL conditions is consistent with the hypothesis that the endogenous activation of 5-HT1B presynaptic receptors modulates circadian behavior by attenuating photic input to the SCN.
血清素（5-羟色胺，5-HT）可在视交叉上核（SCN）中视网膜终末的5-HT1B受体上发挥突触前作用，抑制谷氨酸释放，从而调节光对昼夜节律行为的影响。5-HT1B受体激动剂：（1）抑制昼夜活动节律的光诱导相移；（2）减弱SCN中光诱导的Fos表达；（3）降低体外培养的SCN神经元中视神经诱发的兴奋性突触后电流的幅度。为了确定5-HT1B突触前受体的功能破坏是否会导致SCN对光的反应增强，在几种不同条件下，对5-HT1B受体基因敲除（KO）小鼠和基因匹配的野生型动物的轮转活动昼夜节律周期（tau）进行了评估。在持续光照（LL）条件下，5-HT1B受体KO小鼠的tau显著大于野生型小鼠。对轮转活动的定量分析显示，在LL条件下，野生型和KO小鼠在总活动量或活动的时间分布上均无差异，这表明观察到的tau增加并非活动减少所致。在持续黑暗条件下，野生型和5-HT1B受体KO小鼠的轮转活动昼夜节律周期相似。此外，在12:12光暗循环中，野生型和5-HT1B受体KO小鼠重新适应提前6小时的相位或在昼夜时间16时对10分钟光脉冲的相移速率方面均未发现差异。5-HT1B受体KO小鼠的SCN昼夜节律时钟对LL条件的增强反应与以下假设一致，即5-HT1B突触前受体的内源性激活通过减弱对SCN的光输入来调节昼夜节律行为。
