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使用自动鼠标触摸屏平台量化中枢神经系统损伤后的认知缺陷。

Use of an Automated Mouse Touchscreen Platform for Quantification of Cognitive Deficits After Central Nervous System Injury.

作者信息

Cotter Katherine M, Bancroft Grace L, Haas Harley A, Shi Raymon, Clarkson Andrew N, Croxall Matthew E, Stowe Ann M, Yun Sanghee, Eisch Amelia J

机构信息

Department of Neurology, Department of Neuroscience, The University of Kentucky, Lexington, KY, USA.

University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Methods Mol Biol. 2023;2616:279-326. doi: 10.1007/978-1-0716-2926-0_21.

Abstract

Analyzing cognitive performance is an important aspect of assessing physiological deficits after stroke or other central nervous system (CNS) injuries in both humans and in basic science animal models. Cognitive testing on an automated touchscreen operant platform began in humans but is now increasingly popular in preclinical studies as it enables testing in many cognitive domains in a highly reproducible way while minimizing stress to the laboratory animal. Here, we describe the step-by-step setup and application of four operant touchscreen tests used on adult mice. In brief, mice are trained to touch a graphical image on a lit screen and initiate subsequent trials for a reward. Following initial training, mice can be tested on tasks that probe performance in many cognitive domains and thus infer the integrity of brain circuits and regions. There are already many outstanding published protocols on touchscreen cognitive testing. This chapter is designed to add to the literature in two specific ways. First, this chapter provides in a single location practical, behind-the-scenes tips for setup and testing of mice in four touchscreen tasks that are useful to assess in CNS injury models: Paired Associates Learning (PAL), a task of episodic, associative (object-location) memory; Location Discrimination Reversal (LDR), a test for mnemonic discrimination (also called behavioral pattern separation) and cognitive flexibility; Autoshaping (AUTO), a test of Pavlovian or classical conditioning; and Extinction (EXT), tasks of stimulus-response and response inhibition, respectively. Second, this chapter summarizes issues to consider when performing touchscreen tests in mouse models of CNS injury. Quantifying gross and fine aspects of cognitive function is essential to improved treatment for brain dysfunction after stroke or CNS injury as well as other brain diseases, and touchscreen testing provides a sensitive, reliable, and robust way to achieve this.

摘要

分析认知表现是评估人类和基础科学动物模型中中风或其他中枢神经系统(CNS)损伤后生理缺陷的一个重要方面。在自动化触摸屏操作平台上进行认知测试始于人类,但现在在临床前研究中越来越受欢迎,因为它能够以高度可重复的方式在许多认知领域进行测试,同时将对实验动物的压力降至最低。在这里,我们描述了在成年小鼠上使用的四种操作触摸屏测试的逐步设置和应用。简而言之,训练小鼠触摸点亮屏幕上的图形图像并启动后续试验以获取奖励。在初始训练之后,可以对小鼠进行多项任务测试,这些任务能够探究许多认知领域的表现,从而推断脑回路和脑区的完整性。关于触摸屏认知测试已经有许多出色的已发表方案。本章旨在以两种特定方式补充现有文献。首先,本章在一个地方提供了在四个触摸屏任务中设置和测试小鼠的实用幕后提示,这些提示对于评估CNS损伤模型很有用:配对联想学习(PAL),一种情景性、联想性(物体 - 位置)记忆任务;位置辨别反转(LDR),一种记忆辨别(也称为行为模式分离)和认知灵活性测试;自动塑造(AUTO),一种巴甫洛夫式或经典条件反射测试;以及消退(EXT),分别是刺激 - 反应和反应抑制任务。其次,本章总结了在CNS损伤小鼠模型中进行触摸屏测试时需要考虑的问题。量化认知功能的总体和精细方面对于改善中风或CNS损伤以及其他脑部疾病后的脑功能障碍治疗至关重要,而触摸屏测试提供了一种敏感、可靠且强大的方法来实现这一点。

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