PDF(Pubmed)
Abstract：
Assessment of spatial learning abilities is central to behavioral neuroscience and a useful tool for animal model validation and drug development. However, biases introduced by the apparatus, environment, or experimentalist represent a critical challenge to the test validity. We have recently developed the Modified Barnes Maze (MBM) task, a spatial learning paradigm that overcomes inherent behavioral biases of animals in the classical Barnes maze. The specific combination of spatial strategies employed by mice is often considered representative of the level of cognitive resources used. Herein, we have developed a convolutional neural network-based classifier of exploration strategies in the MBM that can effectively provide researchers with enhanced insights into cognitive traits in mice. Following validation, we compared the learning performance of female and male C57BL/6J mice, as well as that of Ts65Dn mice, a model of Down syndrome, and 5xFAD mice, a model of Alzheimer\'s disease. Male mice exhibited more effective navigation abilities than female mice, reflected in higher utilization of effective spatial search strategies. Compared to wildtype controls, Ts65Dn mice exhibited delayed usage of spatial strategies despite similar success rates in completing this spatial task. 5xFAD mice showed increased usage of non-spatial strategies such as Circling that corresponded to higher latency to reach the target and lower success rate. These data exemplify the need for deeper strategy classification tools in dissecting complex cognitive traits. In sum, we provide a machine-learning-based strategy classifier that extends our understanding of mice\'s spatial learning capabilities while enabling a more accurate cognitive assessment.
摘要：
空间学习能力的评估是行为神经科学的核心，也是动物模型验证和药物开发的有用工具。然而,仪器引入的偏见，环境,或实验主义者代表了测试有效性的关键挑战。我们最近开发了改良的巴恩斯迷宫（MBM）任务，一种空间学习范式，克服了经典巴恩斯迷宫中动物固有的行为偏见。小鼠采用的空间策略的特定组合通常被认为代表所使用的认知资源水平。在这里，我们在MBM中开发了一种基于卷积神经网络的探索策略分类器，可以有效地为研究人员提供对小鼠认知特征的更深入的见解。验证后，我们比较了雌性和雄性C57BL/6J小鼠的学习表现，以及Ts65Dn小鼠，唐氏综合症的模型，和5xFAD小鼠，阿兹海默症的模型.雄性小鼠比雌性小鼠表现出更有效的导航能力，反映在有效空间搜索策略的更高利用率上。与野生型对照相比，尽管Ts65Dn小鼠完成该空间任务的成功率相似，但仍表现出空间策略的延迟使用。5xFAD小鼠显示出非空间策略(例如循环)的使用增加,这对应于较高的等待时间以达到目标和较低的成功率。这些数据表明，在剖析复杂的认知特征时，需要更深入的策略分类工具。总之,我们提供了一个基于机器学习的策略分类器，扩展了我们对小鼠空间学习能力的理解，同时实现了更准确的认知评估。
