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

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Neural Repair

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.

Katherine M. Cotter, Grace L. Bancroft, and Harley A. Haas shared first-authorship for this chapter

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Acknowledgments

NIH (NS 088555-07A1, PI: AMS), NASA (80NSSC21K0814, PI: SY), University of Pennsylvania (Dept Radiation Oncology Pilot Grant, co-PI: AJE; Undergraduate Research Foundation, PI: SY; Trainees: GLB, HAH), the Brain and Behavior Research Foundation (2019 NARSAD Young Investigator Grant, PI: SY), Children Hospital of Philadelphia (2022 Forderer Grant, co-PI: SY).

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Cotter, K.M. et al. (2023). Use of an Automated Mouse Touchscreen Platform for Quantification of Cognitive Deficits After Central Nervous System Injury. In: Karamyan, V.T., Stowe, A.M. (eds) Neural Repair. Methods in Molecular Biology, vol 2616. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2926-0_21

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