Rogers Jake, Churilov Leonid, Hannan Anthony J, Renoir Thibault
Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia.
Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; School of Mathematical and Geospatial Sciences, RMIT University, Melbourne, VIC, Australia.
Neurobiol Learn Mem. 2017 Mar;139:37-49. doi: 10.1016/j.nlm.2016.12.007. Epub 2016 Dec 15.
Using a Matlab classification algorithm, we demonstrate that a highly salient distal cue array is required for significantly increased likelihoods of spatial search strategy selection during Morris water maze spatial learning. We hypothesized that increased spatial search strategy selection during spatial learning would be the key measure demonstrating the formation of an allocentric map to the escape location. Spatial memory, as indicated by quadrant preference for the area of the pool formally containing the hidden platform, was assessed as the main measure that this allocentric map had formed during spatial learning. Our C57BL/6J wild-type (WT) mice exhibit quadrant preference in the highly salient cue paradigm but not the low, corresponding with a 120% increase in the odds of a spatial search strategy selection during learning. In contrast, quadrant preference remains absent in serotonin 1A receptor (5-HTR) knockout (KO) mice, who exhibit impaired search strategy selection during spatial learning. Additionally, we also aimed to assess the impact of the quality of the distal cue array on the spatial learning curves of both latency to platform and path length using mixed-effect regression models and found no significant associations or interactions. In contrast, we demonstrated that the spatial learning curve for search strategy selection was absent during training in the low saliency paradigm. Therefore, we propose that allocentric search strategy selection during spatial learning is the learning parameter in mice that robustly indicates the formation of a cognitive map for the escape goal location. These results also suggest that both latency to platform and path length spatial learning curves do not discriminate between allocentric and egocentric spatial learning and do not reliably predict spatial memory formation. We also show that spatial memory, as indicated by the absolute time in the quadrant formerly containing the hidden platform alone (without reference to the other areas of the pool), was not sensitive to cue saliency or impaired in 5-HTR KO mice. Importantly, in the absence of a search strategy analysis, this suggests that to establish that the Morris water maze has worked (i.e. control mice have formed an allocentric map to the escape goal location), a measure of quadrant preference needs to be reported to establish spatial memory formation. This has implications for studies that claim hippocampal functioning is impaired using latency to platform or path length differences within the existing Morris water maze literature.
使用Matlab分类算法,我们证明,在莫里斯水迷宫空间学习过程中,要显著提高空间搜索策略选择的可能性,需要一个高度显著的远端线索阵列。我们假设,空间学习过程中空间搜索策略选择的增加将是证明形成以目标位置为中心的地图的关键指标。空间记忆通过对正式包含隐藏平台的水池区域的象限偏好来表示,被评估为在空间学习过程中这种以目标位置为中心的地图已经形成的主要指标。我们的C57BL/6J野生型(WT)小鼠在高度显著线索范式中表现出象限偏好,但在低显著线索范式中则没有,这与学习过程中空间搜索策略选择的几率增加120%相对应。相比之下,血清素1A受体(5-HTR)基因敲除(KO)小鼠仍然没有象限偏好,它们在空间学习过程中表现出搜索策略选择受损。此外,我们还旨在使用混合效应回归模型评估远端线索阵列的质量对到达平台的潜伏期和路径长度这两个空间学习曲线的影响,结果未发现显著的关联或相互作用。相反,我们证明在低显著性范式训练期间,搜索策略选择的空间学习曲线不存在。因此,我们提出,在空间学习过程中以目标位置为中心的搜索策略选择是小鼠学习参数,它有力地表明了针对逃生目标位置的认知地图的形成。这些结果还表明,到达平台的潜伏期和路径长度空间学习曲线在以目标位置为中心和以自我为中心的空间学习之间没有区别,也不能可靠地预测空间记忆的形成。我们还表明,仅通过在以前包含隐藏平台的象限中的绝对时间(不参考水池的其他区域)表示的空间记忆,对线索显著性不敏感,在5-HTR KO小鼠中也没有受损。重要的是,在没有搜索策略分析的情况下,这表明要确定莫里斯水迷宫是否起作用(即对照小鼠是否已形成针对逃生目标位置的以目标位置为中心的地图),需要报告象限偏好的指标来确定空间记忆的形成。这对现有莫里斯水迷宫文献中使用到达平台的潜伏期或路径长度差异来声称海马功能受损的研究有影响。