Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Ave., Huntington, WV, 25703, USA.
Department of Psychology, University of Memphis, 400 Innovation Drive, Memphis, TN, 38111, USA.
Sci Rep. 2022 Jan 7;12(1):69. doi: 10.1038/s41598-021-03850-3.
Working memory and pattern separation are fundamental cognitive abilities which, when impaired, significantly diminish quality of life. Discovering genetic mechanisms underlying innate and disease-induced variation in these cognitive abilities is a critical step towards treatments for common and devastating neurodegenerative conditions such as Alzheimer's disease. In this regard, the trial-unique nonmatching-to-location assay (TUNL) is a touchscreen operant conditioning procedure allowing simultaneous quantification of working memory and pattern separation in mice and rats. In the present study, we used the TUNL assay to quantify these cognitive abilities in C57BL/6J and DBA/2J mice. These strains are the founders of the BXD recombinant inbred mouse panel which enables discovery of genetic mechanisms underlying phenotypic variation. TUNL testing revealed that pattern separation was significantly influenced by mouse strain, whereas working memory was not. Moreover, horizontal distance and vertical distance between choice-phase stimuli had dissociable effects on TUNL performance. These findings provide novel data on mouse strain differences in pattern separation and support previous findings of equivalent working memory performance in C57BL/6J and DBA/2J mice. Although working memory of the BXD founder strains was equivalent in this study, working memory of BXD strains may be divergent because of transgressive segregation. Collectively, data presented here indicate that pattern separation is heritable in the mouse and that the BXD panel can be used to identify mechanisms underlying variation in pattern separation.
工作记忆和模式分离是基本的认知能力，当这些能力受损时，会显著降低生活质量。发现这些认知能力中先天和疾病引起的变异的遗传机制是治疗常见和毁灭性神经退行性疾病（如阿尔茨海默病）的关键步骤。在这方面，独特的试验非匹配定位测定（TUNL）是一种触摸屏操作性条件测定程序，可同时定量测定小鼠和大鼠的工作记忆和模式分离。在本研究中，我们使用 TUNL 测定法来定量测定 C57BL/6J 和 DBA/2J 小鼠的这些认知能力。这些品系是 BXD 重组近交系小鼠品系的创始人，该品系能够发现表型变异的遗传机制。TUNL 测试表明，模式分离明显受到小鼠品系的影响，而工作记忆则不受影响。此外，选择阶段刺激的水平距离和垂直距离对 TUNL 性能有不同的影响。这些发现提供了关于模式分离中小鼠品系差异的新数据，并支持了 C57BL/6J 和 DBA/2J 小鼠工作记忆表现相当的先前发现。尽管在这项研究中 BXD 创始人品系的工作记忆相当，但由于超越分离，BXD 品系的工作记忆可能存在差异。总的来说，这里呈现的数据表明模式分离在小鼠中是可遗传的，并且 BXD 面板可以用于识别模式分离变异的机制。
