BEHAVIORAL AND CELLULAR-RESPONSES TO LIGHT OF THE CIRCADIAN SYSTEM OF TAU MUTANT AND WILD-TYPE SYRIAN-HAMSTERS
BEHAVIORAL AND CELLULAR-RESPONSES TO LIGHT OF THE CIRCADIAN SYSTEM OF TAU MUTANT AND WILD-TYPE SYRIAN-HAMSTERS
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DOI：
10.1016/0306-4522(94)00403-r
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发表时间：
1995-03-01
期刊：
影响因子：
3.3
通讯作者：
HASTINGS, MH
中科院分区：
文献类型：
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作者：
GROSSE, J;LOUDON, ASI;HASTINGS, MH
tau突变缩短了自由运行的昼夜节律的活动节奏的叙利亚仓鼠从野生型的24小时左右，在纯合子突变体的20小时。本研究的目的是研究光脉冲对野生型和突变型仓鼠视交叉上核c-fos的活动节律和表达的影响。这将使确定主观昼夜的相对持续时间成为可能，从而进一步表征突变对昼夜节律周期的影响。呈现光脉冲（15分钟）的动物保持在昏暗的红光7至10天诱导的相位依赖性的变化，在活动的开始。在主观的一天（不活跃的阶段），有没有光后，无论是正常或突变动物的活动节奏的影响。在主观夜间早期（即活动期开始后），光脉冲在两种表型中诱导约一个昼夜节律小时的相位延迟。然而，后来在主观的夜间光脉冲引起的活动节奏的相位提前。两种表型之间的提前相移的幅度差异很大，野生型通常显示约一个昼夜节律小时的变化，而突变体显示高达12个昼夜节律小时的更大的进展。在这两种菌株中，在昼夜节律时间22光照后观察到进展，但在昼夜节律时间24光照后观察不到进展。因此，在突变体和野生型中，主观夜晚的相对持续时间是相当的，即大约11个昼夜节律小时。为了检查在不同昼夜节律时相的立即早期基因c-fos的光诱导表达，动物在与它们接受第一次相同的昼夜节律时间接受第二次光脉冲（15分钟）或对照“暗脉冲”，但要晚7到10天。在脉冲开始后1小时灌注它们，并处理大脑用于Fos的免疫细胞化学检测，Fos是c-fos的蛋白产物。接受暗脉冲的动物表现出最小的Fos免疫反应性视交叉上核，无论昼夜节律的时间介绍的刺激。在主观的一天（昼夜时间4-11），光诱导非常小的Fos免疫反应。相比之下，在主观的夜晚（昼夜节律时间12后）的光诱导的Fos免疫反应性在腹外侧，视网膜受体区域的视交叉上核的野生型和突变动物的密集模式。Fos诱导的阶段延伸到整个主观夜晚，并与活动开始和抵消密切相关。在主观晚/早主观天（昼夜节律时间24-3）有一个显着的相关性之间的时间的光脉冲相对于活动偏移和Fos免疫反应核的数目在视交叉上核。总体而言，Fos诱导阶段的相对持续时间在野生型和突变体之间没有显着差异。这些发现表明，由两个标准定义的主观白天和黑夜的相对长度，行为相移和c-fos的表达是相同的，在昼夜节律小时，在野生型和突变动物。这与tau突变加速昼夜节律起搏器的观点一致，在纯合子中，它由24个昼夜节律小时组成，每个小时只有50个太阳分的持续时间。
The tau mutation shortens the free-running circadian period of the activity rhythm of the Syrian hamster from around 24 h in the wild-type, to 20 h in the homozygous mutant. The aim of this study was to examine the effects of light pulses on the activity rhythms and expression of c-fos in the suprachiasmatic nuclei of wild-type and mutant hamsters. This would make it possible to determine the relative durations of subjective day and night, and thereby characterize further the effect of the mutation upon the circadian cycle. Presentation of light pulses (15 min) to animals kept in dim red light for seven to 10 days induced phase-dependent shifts in the onset of activity. During subjective day (inactive phase) there was no effect of light upon the activity rhythm of either normal or mutant animals. Early in subjective night (i.e. after the start of the active phase), light pulses induced phase delays of approximately one circadian hour in both phenotypes. However, later in subjective night light pulses induced phase advances in activity rhythms. The magnitude of the advance phase shifts differed considerably between the two phenotypes, with the wild-types typically showing shifts of about one circadian hour, while the mutants showed much larger advances of up to 12 circadian hours. In both strains, advances were observed following light at circadian time 22 but not after light at circadian time 24. The relative duration of subjective night was therefore comparable in the mutants and wild-types i.e. around 11 circadian hours.In order to examine the light-induced expression of the immediate early gene c-fos at different circadian phases, animals received a second light pulse (15 min) or a control ''dark pulse'' at the same circadian time as they had received the first, but seven to 10 circadian days later. They were perfused 1 h after the start of the pulse and brains processed for the immunocytochemical detection of Fos, the protein product of c-fos. Animals receiving dark pulses showed minimal Fos immunoreactivity in the suprachiasmatic nucleus, regardless of the circadian time of presentation of the stimulus. During subjective day (circadian times 4-11), light induced very little Fos-immunoreactivity. In contrast, light presented during subjective night (after circadian time 12) induced a dense pattern of Fos immunoreactivity in the ventrolateral, retino-recipient region of the suprachiasmatic nucleus of both wild-type and mutant animals. The phase of Fos-induction extended throughout subjective night and was closely linked both to activity onset and offset. During late subjective night/early subjective day (circadian times 24-3) there was a significant correlation between the timing of the light pulse relative to activity offset and the number of Fos immunoreactive nuclei in the suprachiasmatic nucleus. Overall, the relative duration of the Fos-inductive phase was not significantly different between wild-types and mutants.These findings suggest that the relative lengths of subjective day and night as defined by two criteria, behavioural phase-shifting and expression of c-fos are the same,in circadian hours, in the wild-type and mutant animals. This is consistent with the view that the tau mutation accelerates the circadian pacemaker, such that in the homozygote it consists of 24 circadian hours, each of only 50 solar min duration.