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Imaging activation of adult-generated granule cells in spatial memory

Nature Protocols volume 2, pages 3033–3044 (2007)Cite this article

Abstract

New neurons are continuously generated in the subgranular zone of the hippocampus throughout adulthood, and there is increasing interest as to whether these new neurons become functionally integrated into memory circuits. This protocol describes the immunohistochemical procedures to visualize the recruitment of new neurons into circuits supporting spatial memory in intact mice. To label adult-generated granule cells, mice are injected with the proliferation marker 5-bromo-2′-deoxyuridine (BrdU). At different delays after BrdU treatment, mice are trained to locate a hidden platform in the Morris water maze, and spatial memory can then be tested in a probe test with the platform removed from the pool. Ninety minutes after this probe test, mice are perfused and tissue is sectioned. Immunohistochemical procedures are used to quantify BrdU-labeled cells and expression of the immediate early gene, Fos. Because Fos expression is regulated by neuronal activity, the degree of overlap between BrdU-labeled and Fos-labeled neurons provides an indication of whether adult-generated granule neurons have been incorporated into spatial memory circuits.

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Figure 1: Long-lasting water maze memory in mice.
Figure 2: Comparison of C57B6/129 and C57B6 mice in the water maze.
Figure 3: Survival of adult-generated granule cells.
Figure 4: Experimental designs.
Figure 5: Examples of Fos- and 5-bromo-2′-deoxyuridine (BrdU)-labeling in the dentate gyrus.

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Acknowledgements

We thank S. Josselyn and M. Sakaguchi for comments on this manuscript. This work was supported by grants from Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council (NSERC) and the EJLB Foundation (P.W.F.). N.K. and A.H.W. were supported by the Hospital for Sick Children Restracomp awards. C.M.T. received support from the Graduate Program in Areas of Basic and Applied Biology (GABBA) and the Portuguese Foundation for Science and Technology (FCT).

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  1. Nohjin Kee, Cátia M Teixeira and Afra H Wang: These authors contributed equally to this work.

Authors and Affiliations

  1. Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, M5G 1X8, Canada

    Nohjin Kee, Cátia M Teixeira, Afra H Wang & Paul W Frankland

  2. Department of Physiology, University of Toronto, Toronto, M5S 1A8, Canada

    Nohjin Kee, Cátia M Teixeira & Paul W Frankland

  3. Institute of Medical Science, University of Toronto, Toronto, M5S 1A8, Canada

    Nohjin Kee, Cátia M Teixeira, Afra H Wang & Paul W Frankland

  4. Graduate Program in Areas of Basic and Applied Biology (GABBA), Universidade do Porto, Porto, 4050–465, Portugal

    Cátia M Teixeira

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Correspondence to Paul W Frankland.

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Kee, N., Teixeira, C., Wang, A. et al. Imaging activation of adult-generated granule cells in spatial memory. Nat Protoc 2, 3033–3044 (2007). https://doi.org/10.1038/nprot.2007.415

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