Assessing spatial pattern separation in rodents using the object pattern separation task

Abstract

Pattern separation is the process of transforming highly similar sensory inputs into distinct, dissimilar representations. It takes place in the hippocampus and is thought to be used in episodic memory. Impaired pattern separation performance has been recognized as a predictor for the development of cognitive impairments such as dementia in humans and as being present in patients with schizophrenia and post-traumatic stress disorder (PTSD). In this protocol, we describe how to implement a simple and robust object pattern separation (OPS) task in mice and rats that we have previously established and validated. This two-trial memory task uses specific object locations so differences in performance can be calibrated with the extent of object movement. Changes in performance are indicative of spatial pattern separation. In contrast to other pattern separation tasks, the OPS task allows detection of spatial pattern separation performance bidirectionally. Furthermore, the OPS task is cheaper and easier to use and interpret than other tasks that use more than two objects or that are touch-screen based. The entire protocol, from vivarium acclimatization to training of the animals, takes ~35–41 d. After successful training, the animals can be tested repeatedly, and three OPS experiments (n = 20–24 per experimental day) can be performed per week. A standard level of expertise in behavioral studies in rodents is sufficient to successfully integrate this paradigm into an existing rodent test battery.

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Fig. 1: Objects, base plate and testing arena used for rats in the OPS paradigm.
Fig. 2: An example of object placement in both the learning trial (T1) and the test trial (T2).
Fig. 3: Flowchart of the OPS task procedure.
Fig. 4: Characteristic OPS task results, showing the d2 indices (mean + s.e.m.) for all five positions of untreated 4-month-old male Wistar rats (average weight = 393 g).

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Acknowledgements

N.P.v.G. is financially supported by Alzheimer Nederland (grant no. WE.03-2017-11).

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Contributions

N.P.v.G. and J.P. designed the general OPS procedure for measuring pattern separation performance in rodents. B.T.J.v.H. and N.P.v.G. performed the experiments and analyzed the data. N.P.v.G. and B.T.J.v.H wrote the manuscript with input from J. P.

Corresponding author

Correspondence to Jos Prickaerts.

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The authors declare no competing interests.

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Related links

Key references using this protocol

1. van Hagen, B. T. J. et al. Behav. Brain Res. 285, 44–52 (2015): https://doi.org/10.1016/j.bbr.2014.10.041

2. van Goethem, N. P. et al. Br. J. Pharmacol. 172, 2532–2543 (2015): https://doi.org/10.1111/bph.13071.

Electronic supplementary material

Supplementary Data

This Excel file shows scoring of the supplementary video files; output and calculations of the parameters are outlined in the troubleshooting table

Supplementary Video 1

An example of a T1 OPS trial of a mouse. Trial duration is 4 min starting immediately upon placement of the mouse in the testing arena. Position 1 is utilized. The same mouse undertaking the T2 trial is shown in Supplementary Video 2 and the scoring and analysis of this trial is shown in the Supplementary Data

Supplementary Video 2

An example of a T2 OPS trial of a mouse. Trial duration is 4 min starting immediately upon placement of the mouse in the testing arena. Position 4 is utilized as a novel object location (right object moved backward to position 4). The same mouse undertaking the T1 trial is shown in Supplementary Video 1 and the scoring and analysis of this trial is shown in Supplementary the Data

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van Goethem, N.P., van Hagen, B.T.J. & Prickaerts, J. Assessing spatial pattern separation in rodents using the object pattern separation task. Nat Protoc 13, 1763–1792 (2018). https://doi.org/10.1038/s41596-018-0013-x

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