Interval Timing Is Intact in Arrhythmic Cry1/Cry2-Deficient Mice
Interval Timing Is Intact in Arrhythmic Cry1/Cry2-Deficient Mice
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DOI：
10.1177/0748730411410026
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发表时间：
2011-08-01
影响因子：
3.5
通讯作者：
Elgersma, Ype
中科院分区：
文献类型：
--
作者：
Papachristos, Efstathios B.;Jacobs, Edwin H.;Elgersma, Ype
及时定位自我是日常生活功能的基础，在精神分裂症等严重致残性神经精神障碍中是缺乏的。大脑在一系列令人印象深刻的天平上记录时间。在识别生物钟的分子机制方面已经取得了很大进展，生物钟是大脑的主时钟，以24小时为尺度运行，使动物能够知道重要事件发生的“一天中的时间”，而不需要参考外部线索。然而，间隔计时的生物学机制--负责持续时间从秒到分钟到小时的机制--仍然是一个谜，一个明显的问题是，是否有一个共同的生物学解决方案来跟踪这两个时间尺度的时间。为了解决这个问题，我们训练了Cry1/Cry2双基因敲除小鼠进行间隔计时任务，持续时间从3秒到27秒不等。小鼠被保持在恒定的光照条件下，以避免任何外源性诱导的日常节律形式。我们观察到，纯合基因敲除的小鼠表现出与对照小鼠一样准确和精确的时间记忆。这表明，Cry1和Cry2基因不是间隔计时器的重要组成部分。此外，间隔定时器的适当校准不依赖于正常的昼夜节律时钟。因此，这两个计时系统可能依赖于不同和独立的生物学机制。
Localizing the self in time is fundamental for daily life functioning and is lacking in severe disabling neuropsychiatric disorders like schizophrenia. Brains keep track of time across an impressive range of scales. Great progress has been made in identifying the molecular machinery of the circadian clock, the brain's master clock that operates on the 24-hour scale and allows animals to know the "time of the day" that important events occur, without referring to external cues. However, the biology of interval timing, the mechanism responsible for durations in the seconds-to-minutes-to-hours range, remains a mystery, and an obvious question is whether there is a common biological solution for keeping track of time across these 2 time scales. To address this, we trained Cry1/Cry2 double knockout mice on an interval timing task with durations that ranged between 3 and 27 seconds. The mice were kept under constant light conditions to avoid any exogenously induced form of daily rhythmicity. We observed that the homozygous knockouts displayed as accurate and precise a temporal memory as the control mice. This suggests that the Cry1 and Cry2 genes are not an important component of the interval timer. Furthermore, proper calibration of the interval timer does not depend on a functional circadian clock. Thus, these 2 timing systems likely rely on different and independent biological mechanisms.