By the effort to identify candidate signaling molecules important for the formation of robust circadian rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, here we characterize the role of α2δ proteins, synaptic molecules initially identified as an auxiliary subunit of the voltage dependent calcium channel, in circadian rhythm formation. In situ hybridization study demonstrated that type 3 α2δ gene (α2δ3) was strongly expressed in the SCN. Mice without this isoform (Cacna2d3^−/−) did not maintain proper circadian locomotor activity rhythms under a constant light (LL) condition, whereas under a constant dark (DD) condition, these mice showed a similar period length and similar light-responsiveness as compared to wild type mice. Reflecting this behavioral phenotype, Cacna2d3^−/− mice showed a severely impaired Per1 expression rhythm in the SCN under LL, but not under DD. Cultured SCN slices from Per1-luc transgenic Cacna2d3^−/− mice revealed reduced synchrony of Per1-luc gene expression rhythms among SCN neurons. These findings suggest that α2δ3 is essential for synchronized cellular oscillations in the SCN and thereby contributes to enhancing the sustainability of circadian rhythms in behavior.

通过努力寻找对哺乳动物昼夜中心在上视神经核（SCN）中形成稳健的昼夜节律重要的候选信号分子，在这里我们表征了α2δ蛋白的作用，突触分子最初被鉴定为电压依赖性的辅助亚基钙通道，在昼夜节律中形成。原位杂交研究表明3型α2δ基因（α2δ3）在SCN中强烈表达。没有这种亚型的小鼠（Cacna2d3 ^-/-）在恒定的光照（LL）条件下不能维持适当的昼夜运动能力节律，而在恒定的黑暗（DD）条件下，与野生型小鼠相比，这些小鼠表现出相似的周期长度和相似的光反应性。反映此行为表型，Cacna2d3 ^-/-小鼠在LL而不是DD下显示SCN中Per1表达节律严重受损。从Per1-luc转基因Cacna2d3 ^-/-小鼠培养的SCN切片显示Per1-luc的同步性降低SCN神经元之间的基因表达节律。这些发现表明α2δ3对于SCN中的同步细胞振荡是必不可少的，从而有助于增强行为的昼夜节律的可持续性。