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A novel 2- and 3-choice touchscreen-based continuous trial-unique nonmatching-to-location task (cTUNL) sensitive to functional differences between dentate gyrus and CA3 subregions of the hippocampus

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Abstract

Rationale

The touchscreen continuous trial-unique non-matching-to-location task (cTUNL) has been developed to optimise a battery of tasks under NEWMEDS (Novel Methods leading to New Medication in Depression and Schizophrenia, http://www.newmeds-europe.com). It offers novel task features of both a practical and a theoretical nature compared to existing touchscreen tasks for spatial working memory.

Objectives

The objective of this study was to determine whether the cTUNL task is sufficiently sensitive to differentiate between dentate gyrus (DG) and CA3 hippocampal subregion contributions to performance.

Methods

The effect of DG and CA3 dysfunction on memory for locations in the cTUNL task was tested. Rats were assessed on versions of the task—two-choice and three-choice—that differed in memory load. Performance was challenged using manipulations of delay and the spatial separation between target and sample locations.

Results

Dysfunction of the DG disrupts performance across both delay and spatial separations in two-choice cTUNL when the delay is variable and unpredictable. Increasing the working memory load (three stimuli) increases sensitivity to DG dysfunction, with deficits apparent at fixed, short delays. In contrast, CA3 dysfunction did not disrupt performance.

Conclusion

Acquisition of cTUNL was rapid, and the task was sensitive to manipulations of delays and separations. A three-choice version of the task was found to be viable. Finally, both the two- and three-choice versions of the task were able to differentiate between limited dysfunction to different areas within the hippocampus. DG dysfunction affected performance when using unpredictable task parameters. CA3 dysfunction did not result in impairment, even at the longest delays tested.

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Acknowledgments

The work leading to these results has received funding from the Innovative Medicines Initiative Joint Undertaking (IMI) under grant agreement n° 115008. IMI is a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations. As part of this project, CAO was funded by Janssen Pharmaceuticals, Inc., of Johnson & Johnson. The authors thank Jytte van Huijstee and Siyu Jiang for valuable assistance with experiments.

Conflict of interest

TJB consults for Campden Instruments Ltd. LMS consults for Campden Instruments Ltd.

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    Authors and Affiliations

    1. Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK

      C. A. Oomen, M. Hvoslef-Eide, D. Kofink, F. Preusser, A. C. Mar, L. M. Saksida & T. J. Bussey

    2. MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK

      C. A. Oomen, M. Hvoslef-Eide, D. Kofink, F. Preusser, A. C. Mar, L. M. Saksida & T. J. Bussey

    3. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Grooteplein Noord 21, 6525 EZ, Nijmegen, The Netherlands

      C. A. Oomen

    4. Department of Neuroscience and Physiology, New York University Medical Center, New York, NY, 10016, USA

      A. C. Mar

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    Correspondence to C. A. Oomen.

    Additional information

    C. A. Oomen and M. Hvoslef-Eide contributed equally to this work.

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    Oomen, C.A., Hvoslef-Eide, M., Kofink, D. et al. A novel 2- and 3-choice touchscreen-based continuous trial-unique nonmatching-to-location task (cTUNL) sensitive to functional differences between dentate gyrus and CA3 subregions of the hippocampus. Psychopharmacology 232, 3921–3933 (2015). https://doi.org/10.1007/s00213-015-4019-6

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