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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Oomen, C., Hvoslef-Eide, M., Kofink, D., Preusser, F., Mar, A., Saksida, L., & Bussey, T. (2015). 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. https://doi.org/10.1007/s00213-015-4019-6
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.newmedseurope. com). It offers novel task features of both a practical and a theoretical nature compared to existing touchscreen tasks for spatial working memory. Objectives: 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 --2-choice and 3-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 2-choice cTUNL when the delay is variable and unpredictable. Increasing the working memory load (3 stimuli) increases sensitivity to DG dysfunction, with deficits apparent at fixed, short delays. In contrast, CA3 dysfunction did not disrupt performance.
spatial working memory, memory load, dentate gyrus, CA3, hippocampus, touchscreen, rat
This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA inkind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). As part of this project, CAO was funded by Janssen Pharmaceuticals, Inc., of Johnson & Johnson.
Wellcome Trust (089703/Z/09/Z)
External DOI: https://doi.org/10.1007/s00213-015-4019-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248911