Ehlen J Christopher, Novak Colleen M, Karom Mary C, Gamble Karen L, Albers H Elliott
Department of Biology, Georgia State University, Atlanta, GA, USA.
J Biol Rhythms. 2008 Feb;23(1):16-25. doi: 10.1177/0748730407310785.
Activation of gamma-aminobutyric acid (GABA) A receptors in the suprachiasmatic nucleus (SCN) resets the circadian clock during the day and inhibits the ability of light to reset the clock at night. Light in turn acts during the day to inhibit the phase-resetting effects of GABA. Some evidence suggests that Period mRNA changes in the SCN are responsible for these interactions between light and GABA. Here, the hypothesis that light and the GABA A receptor interact by altering the expression of Period 1 and/or Period 2 mRNA in the SCN is tested. The GABA A agonist muscimol was injected near the SCN just prior to a light pulse, during the mid-subjective day and the early and late subjective night. Changes in Period 1 and Period 2 mRNA were measured in the SCN by in situ hybridization. Light-induced Period 1 mRNA was inhibited by GABA A receptor activation in the early and late subjective night, while Period 2 mRNA was only inhibited during the late night. During the subjective day, light had no effect on the ability of muscimol to suppress Period 1 mRNA hybridization signal. Thus, light and GABA A receptor activation inhibit each other's ability to induce behavioral phase shifts throughout the subjective day and night. However, only in the late night are these behavioral effects correlated with changes in Period gene expression. Together, our data support the hypothesis that the interacting effects of light and GABA are the result of the opposing actions of these stimuli on Period mRNA, but only during the subjective night.
视交叉上核(SCN)中γ-氨基丁酸(GABA)A受体的激活在白天重置昼夜节律时钟,并在夜间抑制光重置时钟的能力。反过来,光在白天起作用以抑制GABA的相位重置效应。一些证据表明,SCN中Period mRNA的变化是光与GABA之间这些相互作用的原因。在此,测试了光和GABA A受体通过改变SCN中Period 1和/或Period 2 mRNA的表达相互作用的假说。在光脉冲之前、主观日中午以及主观夜的早期和晚期,将GABA A激动剂蝇蕈醇注射到SCN附近。通过原位杂交测量SCN中Period 1和Period 2 mRNA的变化。在主观夜的早期和晚期,光诱导的Period 1 mRNA受到GABA A受体激活的抑制,而Period 2 mRNA仅在深夜受到抑制。在主观日期间,光对蝇蕈醇抑制Period 1 mRNA杂交信号的能力没有影响。因此,在整个主观日和夜,光和GABA A受体激活相互抑制对方诱导行为相位偏移的能力。然而,只有在深夜,这些行为效应才与Period基因表达的变化相关。总之,我们的数据支持以下假说:光和GABA的相互作用效应是这些刺激对Period mRNA的相反作用的结果,但仅在主观夜期间如此。