Petersen Christian C, Mistlberger Ralph E
Department of Psychology, Simon Fraser University, Burnaby, British Columbia, Canada.
J Biol Rhythms. 2017 Aug;32(4):295-308. doi: 10.1177/0748730417716231. Epub 2017 Jun 26.
The mechanisms that enable mammals to time events that recur at 24-h intervals (circadian timing) and at arbitrary intervals in the seconds-to-minutes range (interval timing) are thought to be distinct at the computational and neurobiological levels. Recent evidence that disruption of circadian rhythmicity by constant light (LL) abolishes interval timing in mice challenges this assumption and suggests a critical role for circadian clocks in short interval timing. We sought to confirm and extend this finding by examining interval timing in rats in which circadian rhythmicity was disrupted by long-term exposure to LL or by chronic intake of 25% DO. Adult, male Sprague-Dawley rats were housed in a light-dark (LD) cycle or in LL until free-running circadian rhythmicity was markedly disrupted or abolished. The rats were then trained and tested on 15- and 30-sec peak-interval procedures, with water restriction used to motivate task performance. Interval timing was found to be unimpaired in LL rats, but a weak circadian activity rhythm was apparently rescued by the training procedure, possibly due to binge feeding that occurred during the 15-min water access period that followed training each day. A second group of rats in LL were therefore restricted to 6 daily meals scheduled at 4-h intervals. Despite a complete absence of circadian rhythmicity in this group, interval timing was again unaffected. To eliminate all possible temporal cues, we tested a third group of rats in LL by using a pseudo-randomized schedule. Again, interval timing remained accurate. Finally, rats tested in LD received 25% DO in place of drinking water. This markedly lengthened the circadian period and caused a failure of LD entrainment but did not disrupt interval timing. These results indicate that interval timing in rats is resistant to disruption by manipulations of circadian timekeeping previously shown to impair interval timing in mice.
哺乳动物用以对以24小时为间隔重复出现的事件(昼夜节律计时)以及秒到分钟范围内任意间隔的事件(间隔计时)进行计时的机制,在计算和神经生物学层面被认为是不同的。最近有证据表明,持续光照(LL)扰乱昼夜节律会消除小鼠的间隔计时,这对这一假设提出了挑战,并表明生物钟在短间隔计时中起着关键作用。我们试图通过研究长期暴露于LL或长期摄入25% DO从而扰乱昼夜节律的大鼠的间隔计时来证实并扩展这一发现。成年雄性Sprague-Dawley大鼠被饲养在明暗(LD)循环环境或LL环境中,直到自由运行的昼夜节律明显被扰乱或消除。然后,对这些大鼠进行15秒和30秒峰值间隔程序的训练和测试,采用限水措施来促使其完成任务。结果发现,LL大鼠的间隔计时未受影响,但训练程序显然挽救了一种微弱的昼夜活动节律,这可能是由于每天训练后15分钟饮水期间出现的暴饮暴食所致。因此,对LL环境中的第二组大鼠限制为每天6餐,每隔4小时安排一次。尽管该组大鼠完全没有昼夜节律,但间隔计时再次未受影响。为了消除所有可能的时间线索,我们使用伪随机时间表对LL环境中的第三组大鼠进行测试。同样,间隔计时仍然准确。最后,在LD环境中测试的大鼠饮用25% DO代替饮用水。这显著延长了昼夜周期并导致LD同步失败,但并未扰乱间隔计时。这些结果表明,大鼠的间隔计时对先前已证明会损害小鼠间隔计时的昼夜计时操纵具有抗性。