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Recoding a cocaine-place memory engram to a neutral engram in the hippocampus

Nature Neuroscience volume 19, pages 564567 (2016) | Download Citation

Abstract

The hippocampus provides the brain's memory system with a subset of neurons holding a map-like representation of each environment experienced. We found in mice that optogenetic silencing those neurons active in an environment unmasked a subset of quiet neurons, enabling the emergence of an alternative map. When applied in a cocaine-paired environment, this intervention neutralized an otherwise long-lasting drug-place preference, showing that recoding a spatial memory engram can alleviate associated maladaptive behavior.

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References

  1. 1.

    , & Nat. Rev. Neurosci. 8, 657–661 (2007).

  2. 2.

    & Brain Res. 34, 171–175 (1971).

  3. 3.

    & Science 261, 1055–1058 (1993).

  4. 4.

    et al. Science 309, 619–623 (2005).

  5. 5.

    Neuron 68, 362–385 (2010).

  6. 6.

    , & Ann. NY Acad. Sci. 1141, 1–21 (2008).

  7. 7.

    & J. Neurosci. 7, 1951–1968 (1987).

  8. 8.

    , & Hippocampus 1, 193–205 (1991).

  9. 9.

    , , , & Science 305, 1295–1298 (2004).

  10. 10.

    & PLoS Biol. 8, e1000403 (2010).

  11. 11.

    , , , & Science 308, 873–876 (2005).

  12. 12.

    , , & Nature 430, 456–459 (2004).

  13. 13.

    & J. Neurosci. 9, 2382–2390 (1989).

  14. 14.

    , & Neuron 70, 109–120 (2011).

  15. 15.

    & J. Neurosci. 28, 14271–14281 (2008).

  16. 16.

    & Cell Rep. 4, 1010–1021 (2013).

  17. 17.

    , & Science 337, 849–853 (2012).

  18. 18.

    , , , & Proc. Natl. Acad. Sci. USA 98, 9386–9390 (2001).

  19. 19.

    et al. Science 341, 387–391 (2013).

  20. 20.

    et al. Nature 513, 426–430 (2014).

  21. 21.

    , , & Front. Mol. Neurosci. 7, 82 (2014).

  22. 22.

    , , & Science 317, 1230–1233 (2007).

  23. 23.

    et al. Front. Syst. Neurosci. 5, 18 (2011).

  24. 24.

    , , , & Nat. Neurosci. 17, 1658–1660 (2014).

  25. 25.

    , , , & J. Neurosci. 19, 274–287 (1999).

  26. 26.

    , , , & J. Neurophysiol. 84, 401–414 (2000).

  27. 27.

    et al. Nat. Neurosci. 15, 1265–1271 (2012).

  28. 28.

    et al. Neuron 82, 872–886 (2014).

  29. 29.

    et al. eLife 3, 04006 (2014).

  30. 30.

    , , & Nat. Neurosci. 13, 995–1002 (2010).

  31. 31.

    & J. Neurosci. 9, 4101–4110 (1989).

  32. 32.

    , , , & Nat. Neurosci. 11, 209–215 (2008).

  33. 33.

    , & J. Neurosci. Methods 220, 149–166 (2013).

  34. 34.

    , , , & Nature 424, 552–556 (2003).

  35. 35.

    & Math USSR-Sbornik 1, 457–483 (1967).

  36. 36.

    , , , & PLoS One 6, e20996 (2011).

  37. 37.

    , , , & J. Comput. Neurosci. 29, 309–325 (2010).

  38. 38.

    , , , & Nat. Neurosci. 12, 919–926 (2009).

  39. 39.

    , & J. Neurosci. Methods 94, 141–154 (1999).

  40. 40.

    IEEE Trans. Neural Netw. 10, 626–634 (1999).

  41. 41.

    , & (2013).

  42. 42.

    , & Neuron 78, 166–180 (2013).

  43. 43.

    , , & Stat. Med. 26, 3997–4008 (2007).

  44. 44.

    , & Neuroreport 14, 2127–2131 (2003).

  45. 45.

    , , & Behav. Pharmacol. 20, 720–730 (2009).

  46. 46.

    , & Brain Res. Rev. 59, 253–277 (2009).

  47. 47.

    , , , & Phil. Trans. R. Soc. Lond. B 369, 20120518 (2014).

  48. 48.

    et al. Nat. Neurosci. 16, 1802–1811 (2013).

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Acknowledgements

We thank P. Somogyi, R. Guillery, P. Brown, H. Barron, A. Morley and V. Lopes-dos-Santos for initial discussion, L. Norman and J. Janson for technical assistance, L. Katona for help with confocal imaging, and E.S. Boyden (Massachusetts Institute of Technology) for sharing the pAAV-CamKII-ArchT-GFP. The use of the c-fos-tTA mouse is disclosed by a material transfer agreement between The Scripps Research Institute and the MRC BNDU at the University of Oxford. This work was supported by the Medical Research Council UK (awards MC_UU_12020/7 and MC_UU_12024/3, both to D.D.) and a Mid-Career Researchers Equipment Grant from the Medical Research Foundation (award C0443 to D.D.).

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Affiliations

  1. Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford, UK.

    • Stéphanie Trouche
    • , Pavel V Perestenko
    • , Gido M van de Ven
    • , Claire T Bratley
    • , Colin G McNamara
    • , Natalia Campo-Urriza
    • , S Lucas Black
    •  & David Dupret
  2. Department of Neuroscience, School of Medicine, Tufts University, Boston, Massachusetts, USA.

    • Leon G Reijmers

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Contributions

S.T. and D.D. designed the experiments. P.V.P. cloned and tested the construct. S.T., N.C.-U., C.T.B. and P.V.P. carried out the experiments. S.T. and S.L.B. performed the cell counting. S.T., G.M.v.d.V., C.T.B., P.V.P., C.G.M. and D.D. analyzed the data. L.G.R. provided the mice and helped with the behavioral protocols. S.T. and D.D. wrote the manuscript. D.D. supervised the project. All of the authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Stéphanie Trouche or David Dupret.

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DOI

https://doi.org/10.1038/nn.4250

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