The touchscreen operant platform for testing working memory and pattern separation in rats and mice

Abstract

The automated touchscreen operant chamber for rats and mice allows for the assessment of multiple cognitive domains within the same testing environment. This protocol presents the location discrimination (LD) task and the trial-unique delayed nonmatching-to-location (TUNL) task, which both assess memory for location. During these tasks, animals are trained to a predefined criterion during 20–40 daily sessions. In LD sessions, touching the same location on the screen is rewarded on consecutive trials, followed by a reversal of location-reward contingencies. TUNL, a working memory task, requires animals to 'nonmatch' to a sample location after a delay. In both the LD and TUNL tasks, spatial similarity can be varied, allowing assessment of pattern separation ability, a function that is thought to be performed by the dentate gyrus (DG). These tasks are therefore particularly useful in animal models of hippocampal, and specifically DG, function, but they additionally permit discernment of changes in pattern separation from those in working memory.

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Figure 1: Flowchart overview of the main features of the touchscreen TUNL task.
Figure 2: Flowchart overview of the intermediate training and performance probe phases of the location discrimination (LD) task.
Figure 3: Average performance of male Lister hooded rats on TUNL probe sessions for different delays and separations.
Figure 4: Average performance of Tnik−/− (n = 12, dashed line) and wild-type (WT) mice of the same background (C57BL/6 × 129S5, n = 8, solid line) on the LD task.

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Acknowledgements

The protocols described here are those used in our laboratory at present, and were written by current members of the group. However, many researchers have contributed to the development of touchscreen tasks and we would like to gratefully acknowledge their contribution. They include S. Bartko, J. Brigman, S. Forwood, C. Graybeal, A. Izquierdo, L. Lyon, A. Marti, K. McAllister, S. McTighe, J. Nithianantharajah, C. Romberg, J. Talpos and B. Winters. The research leading to these results has received support from the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008, of which resources are composed of a European Federation of Pharmaceutical Industries and Associations in-kind contribution and financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013); and the Wellcome Trust/Medical Research Council (089703/Z/09/Z) and Alzheimer's Research UK (ART/PG2006/5). A.E.H. receives funding from the European Union Seventh Framework Programme under grant agreement nos. 241995 (Project 'GENCODYS') and 242167 (Project 'SYNSYS').

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All authors contributed to the writing of this manuscript. C.A.O. coordinated this effort.

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Correspondence to Charlotte A Oomen.

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L.M.S. and T.J.B. consult for Campden Instruments, Ltd. A.E.H. is an employee of Synome, Ltd.

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Oomen, C., Hvoslef-Eide, M., Heath, C. et al. The touchscreen operant platform for testing working memory and pattern separation in rats and mice. Nat Protoc 8, 2006–2021 (2013). https://doi.org/10.1038/nprot.2013.124

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