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A novel touchscreen-automated paired-associate learning (PAL) task sensitive to pharmacological manipulation of the hippocampus: a translational rodent model of cognitive impairments in neurodegenerative disease

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Abstract

Rationale

Paired-associate learning (PAL), as part of the Cambridge Neuropsychological Test Automated Battery, is able to predict who from an at-risk population will develop Alzheimer’s disease. Schizophrenic patients are also impaired on this same task. An automated rodent model of PAL would be extremely beneficial in further research into Alzheimer’s disease and schizophrenia.

Objective

The objective of this study was to develop a PAL task using touchscreen-equipped operant boxes and test its sensitivity to manipulations of the hippocampus, a brain region of interest in both Alzheimer’s disease and schizophrenia.

Materials and methods

Previous work has shown that spatial and non-spatial memory can be tested in touchscreen-equipped operant boxes. Using this same apparatus, rats were trained on two variants of a PAL task differing only in the nature of the S− (the unrewarded stimuli, a combination of image and location upon the screen). Rats underwent cannulation of the dorsal hippocampus, and after recovery were tested under the influence of intra-hippocampally administered glutamatergic and cholinergic antagonists while performing the PAL task.

Results

Impairments were seen after the administration of glutamatergic antagonists, but not cholinergic antagonists, in one of the two versions of PAL.

Conclusions

De-activation of the hippocampus caused impairments in a PAL task. The selective nature of this effect (only one of the two tasks was impaired), suggests the effect is specific to cognition and cannot be attributed to gross impairments (changes in visual learning). The pattern of results suggests that rodent PAL may be suitable as a translational model of PAL in humans.

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Acknowledgements

This work was supported by a grant to TJB and LMS from the Wellcome Trust, Number 071493/Z/03/Z. John Talpos was funded by a Merck, Sharp, & Dohme Ph.D. fellowship.

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Authors and Affiliations

  1. Department of Experimental Psychology, University of Cambridge, Cambridge, UK

    J. C. Talpos, L. M. Saksida & T. J. Bussey

  2. Department of Psychology, University of Guelph, Guelph, Canada

    B. D. Winters

  3. Merck, Sharp & Dohme, Harlow, UK

    R. Dias

  4. The MRC and Wellcome Trust Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK

    L. M. Saksida & T. J. Bussey

  5. Eli Lilly, Erl Wood Manor, Sunninghill Road, Windlesham, UK, GU20 6PH

    J. C. Talpos

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  1. J. C. Talpos
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  2. B. D. Winters
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  4. L. M. Saksida
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  5. T. J. Bussey
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Correspondence to J. C. Talpos.

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Talpos, J.C., Winters, B.D., Dias, R. et al. A novel touchscreen-automated paired-associate learning (PAL) task sensitive to pharmacological manipulation of the hippocampus: a translational rodent model of cognitive impairments in neurodegenerative disease. Psychopharmacology 205, 157–168 (2009). https://doi.org/10.1007/s00213-009-1526-3

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  • DOI: https://doi.org/10.1007/s00213-009-1526-3

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