Sollars Patricia J, Ogilvie Malcolm D, Simpson Anne M, Pickard Gary E
Division of Neuroscience, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
J Biol Rhythms. 2006 Feb;21(1):21-32. doi: 10.1177/0748730405283765.
The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that receives glutamatergic afferents from the retina and serotonergic afferents from the midbrain. Activation of presynaptic serotonin 1B (5-HT1B) receptors on retinal terminals in the SCN inhibits retinohypothalamic neurotransmission and light-induced behavioral phase shifts. To assess the role of 5-HT1B receptors in photic entrainment, 5-HT1B receptor knockout (5-HT1B KO) and wild-type (WT) mice were maintained in non-24 h L:D cycles (T cycles). WT mice entrained to T = 21 h and T = 22 h cycles, whereas 5-HT1B KO animals did not. 5-HT1B KO animals did entrain to T = 23 h and T = 26 h cycles, although their phase angle of entrainment was altered compared to WT animals. 5-HT1B KO mice were significantly more phase delayed under T = 23 h conditions and significantly more phase advanced under T = 26 h conditions compared to WT mice. When 5-HT1B KO mice were housed in a T = 23 h short-day photoperiod (9.5L:13.5D), the delayed phase angle of entrainment was more pronounced. Light-induced phase shifts were reduced in 5-HT1B KO mice, consistent with their behavior in T cycles, suggesting an attenuated response to light. Based on previous work, this attenuated response to light might not have been predicted but can be explained by consideration of GABAergic mechanisms within the SCN. Phase-delayed circadian rhythms during the short days of winter are characteristic of patients suffering from seasonal affective disorder, and 5-HT has been implicated in its pathophysiology. The 5-HT1B KO mouse may be useful for investigating the altered entrainment evident during this serious mood disorder.
下丘脑视交叉上核（SCN）是一个昼夜节律振荡器，它接收来自视网膜的谷氨酸能传入神经和来自中脑的5-羟色胺能传入神经。SCN中视网膜终末上的突触前5-羟色胺1B（5-HT1B）受体的激活会抑制视网膜下丘脑神经传递以及光诱导的行为相位偏移。为了评估5-HT1B受体在光同步化中的作用，将5-HT1B受体敲除（5-HT1B KO）小鼠和野生型（WT）小鼠置于非24小时的光暗循环（T循环）中。WT小鼠能同步到T = 21小时和T = 22小时的循环，而5-HT1B KO动物则不能。5-HT1B KO动物确实能同步到T = 23小时和T = 26小时的循环，尽管与WT动物相比，它们的同步相位角发生了改变。与WT小鼠相比，5-HT1B KO小鼠在T = 23小时条件下相位延迟明显更多，在T = 26小时条件下相位提前明显更多。当5-HT1B KO小鼠饲养在T = 23小时的短日照光周期（9.5小时光照：13.5小时黑暗）中时，延迟的同步相位角更为明显。5-HT1B KO小鼠的光诱导相位偏移减少，这与其在T循环中的行为一致，表明对光的反应减弱。根据先前的研究工作，这种对光的减弱反应可能无法预测，但可以通过考虑SCN内的γ-氨基丁酸能机制来解释。冬季短日照期间相位延迟的昼夜节律是季节性情感障碍患者的特征，并且5-羟色胺已被认为与该病的病理生理学有关。5-HT1B KO小鼠可能有助于研究这种严重情绪障碍期间明显改变的同步化情况。
