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The spontaneous location recognition task for assessing spatial pattern separation and memory across a delay in rats and mice

Nature Protocols volume 16, pages 5616–5633 (2021)Cite this article

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Abstract

Keeping similar memories distinct from one another is a critical cognitive process without which we would have difficulty functioning in everyday life. Memories are thought to be kept distinct through the computational mechanism of pattern separation, which reduces overlap between similar input patterns to amplify differences among stored representations. At the behavioral level, impaired pattern separation has been shown to contribute to memory deficits seen in neuropsychiatric and neurodegenerative diseases, including Alzheimer’s disease, and in normal aging. This protocol describes the use of the spontaneous location recognition (SLR) task in mice and rats to behaviorally assess spatial pattern separation ability. This two-phase spontaneous memory task assesses the extent to which animals can discriminate and remember object locations presented during the encoding phase. Using three configurations of the task, the similarity of the to-be-remembered locations can be parametrically manipulated by altering the spatial positions of objects—dissimilar, similar or extra similar—to vary the load on pattern separation. Unlike other pattern separation tasks, SLR varies the load on pattern separation during encoding, when pattern separation is thought to occur. Furthermore, SLR can be used in standard rodent behavioral facilities with basic expertise in rodent handling. The entire protocol takes ~20 d from habituation to testing of the animals on all three task configurations. By incorporating breaks between testing, and varying the objects used as landmarks, animals can be tested repeatedly, increasing experimental power by allowing for within-subjects manipulations.

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Fig. 1: SLR task to assess pattern separation in rats or mice.
Fig. 2: Experimental data showing the effect of manipulations that reduce or augment hippocampal plasticity on SLR performance.
Fig. 3: SLR apparatus setup for rats and mice.
Fig. 4: Objects used in SLR tests, showing examples of objects that we have previously used successfully with mice.
Fig. 5: SLR test performance in rats and mice.
Fig. 6: Flowchart of the experimental protocol for rats and mice.

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Data availability

The authors declare that the main data supporting the findings of this protocol are available within the article and and/or are already published and included with permission. Extra data are available from the corresponding author upon request. Source data are provided with this paper.

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Acknowledgements

The protocols described are those that are currently used in our laboratories, and they were written by current members of the research group. The research leading to these results has received support from: Canada First Research Excellence Fund BrainsCAN; Natural Sciences and Engineering Research Council (NSERC); Biotechnology and Biological Sciences Research Council (grant BB/G019002/1); Innovative Medicine Initiative Joint Undertaking under grant agreement number 115008, of which resources are composed of European Federation of Pharmaceutical Industries and Associations (EFPIA) in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013); Australian Research Council (DE140101301 and DP180101974).

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada

    Amy C. Reichelt, Paul A. S. Sheppard, Lisa M. Saksida & Timothy J. Bussey

  2. Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada

    Amy C. Reichelt, Paul A. S. Sheppard, Lisa M. Saksida & Timothy J. Bussey

  3. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia

    Amy C. Reichelt

  4. Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Quebec, Canada

    Cecilia P. Kramar

  5. Neuroscience Graduate Program, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada

    Olivia R. Ghosh-Swaby

  6. Department of Psychology, Simon Fraser University, Burnaby, British Columbia, Canada

    Brianne A. Kent

  7. Instituto de Neurociencia Cognitiva y Traslacional (CONICET-INECO-Universidad Favaloro), Buenos Aires, Argentina

    Pedro Bekinschtein

  8. Brain and Mind Institute, Western University, London, Ontario, Canada

    Lisa M. Saksida & Timothy J. Bussey

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

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Correspondence to Amy C. Reichelt or Timothy J. Bussey.

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Key references using this protocol

Bekinschtein, P. et al. Cell Rep. 5, 759–768 (2013): https://doi.org/10.1016/j.celrep.2013.09.027

Bonafina, A. et al. Cell Rep. 29, 4308–4319 (2019): https://doi.org/10.1016/j.celrep.2019.11.100

Reichelt, A.C. et al. Learn. Mem. 23, 386–390 (2016): https://doi.org/10.1101/lm.042416.116

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Reichelt, A.C., Kramar, C.P., Ghosh-Swaby, O.R. et al. The spontaneous location recognition task for assessing spatial pattern separation and memory across a delay in rats and mice. Nat Protoc 16, 5616–5633 (2021). https://doi.org/10.1038/s41596-021-00627-w

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