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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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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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).
The authors declare no competing interests.
Peer review information Nature Protocols thanks Arjan Blokland, Thomas Freret and the other, anonymous reviewer(s) for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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