The relative lack of sensitive and clinically valid tests of rodent behavior might be one of the reasons for the limited success of the clinical translation of preclinical Alzheimer's disease (AD) research findings. There is a general interest in innovative behavioral methodology, and protocols have been proposed for touchscreen operant chambers that might be superior to existing cognitive assessment methods. We assessed and analyzed touchscreen performance in several novel ways to examine the possible occurrence of early signs of prefrontal (PFC) functional decline in the APP/PS1 mouse model of AD. Touchscreen learning performance was compared between APP/PS1‐21 mice and wildtype littermates on a C57BL/6J background at 3, 6 and 12 months of age in parallel to the assessment of spatial learning, memory and cognitive flexibility in the Morris water maze (MWM). We found that older mice generally needed more training sessions to complete the touchscreen protocol than younger ones. Older mice also displayed defects in MWM working memory performance, but touchscreen protocols detected functional changes beginning at 3 months of age. Histological changes in PFC of APP/PS1 mice indeed occurred as early as 3 months. Our results suggest that touchscreen operant protocols are more sensitive to PFC dysfunction, which is of relevance to the use of these tasks and devices in preclinical AD research and experimental pharmacology.

中文翻译：

---

触摸屏操作室与水迷宫检测小鼠早期前额叶功能障碍的比较。

对啮齿动物行为的敏感和临床有效测试的相对缺乏可能是临床前阿尔茨海默病 (AD) 研究结果的临床转化成功有限的原因之一。人们普遍对创新的行为方法感兴趣，并且已经为触摸屏操作室提出了可能优于现有认知评估方法的协议。我们以几种新颖的方式评估和分析了触摸屏性能，以检查 AD 的 APP/PS1 小鼠模型中可能出现的前额叶 (PFC) 功能衰退的早期迹象。在 3、6 和 12 个月大的 C57BL/6J 背景下，在评估空间学习的同时，比较了 APP/PS1-21 小鼠和野生型同窝小鼠的触摸屏学习表现，莫里斯水迷宫 (MWM) 中的记忆和认知灵活性。我们发现年长的老鼠通常比年轻的老鼠需要更多的训练来完成触摸屏协议。年长的老鼠也表现出 MWM 工作记忆性能的缺陷，但触摸屏协议检测到从 3 个月大时开始的功能变化。APP/PS1 小鼠 PFC 的组织学变化确实早在 3 个月就发生了。我们的结果表明，触摸屏操作协议对 PFC 功能障碍更敏感，这与在临床前 AD 研究和实验药理学中使用这些任务和设备有关。但触摸屏协议检测到从 3 个月大时开始的功能变化。APP/PS1 小鼠 PFC 的组织学变化确实早在 3 个月就发生了。我们的结果表明，触摸屏操作协议对 PFC 功能障碍更敏感，这与在临床前 AD 研究和实验药理学中使用这些任务和设备有关。但触摸屏协议检测到从 3 个月大时开始的功能变化。APP/PS1 小鼠 PFC 的组织学变化确实早在 3 个月就发生了。我们的结果表明，触摸屏操作协议对 PFC 功能障碍更敏感，这与在临床前 AD 研究和实验药理学中使用这些任务和设备有关。