Department of Molecular Neurobiology, University of Groningen, The Netherlands.
Sleep. 2010 Nov;33(11):1465-73. doi: 10.1093/sleep/33.11.1465.
dissociable cognitive strategies are used for place navigation. Spatial strategies rely on the hippocampus, an area important for flexible integration of novel information. Response strategies are more rigid and involve the dorsal striatum. These memory systems can compensate for each other in case of temporal or permanent damage. Sleep deprivation has adverse effects on hippocampal function. However, whether the striatal memory system can compensate for sleep-deprivation-induced hippocampal impairments is unknown.
with a symmetrical maze paradigm for mice, we examined the effect of sleep deprivation on learning the location of a food reward (training) and on learning that a previously nonrewarded arm was now rewarded (reversal training).
five hours of sleep deprivation after each daily training session did not affect performance during training. However, in contrast with controls, sleep-deprived mice avoided a hippocampus-dependent spatial strategy and preferentially used a striatum-dependent response strategy. In line with this, the training-induced increase in phosphorylation of the transcription factor cAMP response-element binding protein (CREB) shifted from hippocampus to dorsal striatum. Importantly, although sleep-deprived mice performed well during training, performance during reversal training was attenuated, most likely due to rigidity of the striatal system they used.
together, these findings suggest that the brain compensates for negative effects of sleep deprivation on the hippocampal memory system by promoting the use of a striatal memory system. However, effects of sleep deprivation can still appear later on because the alternative learning mechanisms and brain regions involved may result in reduced flexibility under conditions requiring adaptation of previously formed memories.
分离认知策略用于空间导航。空间策略依赖于海马体,海马体对于灵活整合新信息非常重要。反应策略则更为僵化,涉及背侧纹状体。这些记忆系统可以在时间或永久性损伤的情况下相互补偿。睡眠剥夺对海马体功能有不良影响。然而,纹状体记忆系统是否可以补偿睡眠剥夺引起的海马体损伤尚不清楚。
我们使用对称迷宫范式对小鼠进行研究,以观察睡眠剥夺对学习食物奖励位置(训练)以及学习以前无奖励的臂现在有奖励(反转训练)的影响。
每天训练后 5 小时的睡眠剥夺并不影响训练期间的表现。然而,与对照组相比,睡眠剥夺的小鼠避免了海马体依赖的空间策略,优先使用纹状体依赖的反应策略。与此一致的是,训练诱导的转录因子 cAMP 反应元件结合蛋白(CREB)磷酸化的增加从海马体转移到背侧纹状体。重要的是,尽管睡眠剥夺的小鼠在训练期间表现良好,但在反转训练期间的表现受到了削弱,这很可能是由于它们所使用的纹状体系统的僵化所致。
这些发现表明,大脑通过促进纹状体记忆系统的使用来补偿睡眠剥夺对海马体记忆系统的负面影响。然而,由于涉及的替代学习机制和大脑区域可能导致在需要适应先前形成的记忆的情况下降低灵活性,因此睡眠剥夺的影响可能仍然会出现。