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The reorganization and reactivation of hippocampal maps predict spatial memory performance

Nature Neuroscience volume 13, pages 9951002 (2010) | Download Citation

Abstract

The hippocampus is an important brain circuit for spatial memory and the spatially selective spiking of hippocampal neuronal assemblies is thought to provide a mnemonic representation of space. We found that remembering newly learnt goal locations required NMDA receptor–dependent stabilization and enhanced reactivation of goal-related hippocampal assemblies. During spatial learning, place-related firing patterns in the CA1, but not CA3, region of the rat hippocampus were reorganized to represent new goal locations. Such reorganization did not occur when goals were marked by visual cues. The stabilization and successful retrieval of these newly acquired CA1 representations of behaviorally relevant places was NMDAR dependent and necessary for subsequent memory retention performance. Goal-related assembly patterns associated with sharp wave/ripple network oscillations, during both learning and subsequent rest periods, predicted memory performance. Together, these results suggest that the reorganization and reactivation of assembly firing patterns in the hippocampus represent the formation and expression of new spatial memory traces.

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References

  1. 1.

    & The Hippocampus as a Cognitive Map (Oxford Univ. Press, 1978).

  2. 2.

    Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol. Rev. 99, 195–231 (1992).

  3. 3.

    Elements of a neurobiological theory of hippocampal function: the role of synaptic plasticity, synaptic tagging and schemas. Eur. J. Neurosci. 23, 2829–2846 (2006).

  4. 4.

    et al. Reversible neural inactivation reveals hippocampal participation in several memory processes. Nat. Neurosci. 2, 898–905 (1999).

  5. 5.

    The Organization of Behavior (Wiley, New York, 1949).

  6. 6.

    Simple memory: a theory for archicortex. Phil. Trans. R. Soc. Lond. B 262, 23–81 (1971).

  7. 7.

    Two-stage model of memory trace formation: a role for “noisy” brain states. Neuroscience 31, 551–570 (1989).

  8. 8.

    , & Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychol. Rev. 102, 419–457 (1995).

  9. 9.

    Perseverative neural processes and consolidation of the memory trace. Psychol. Bull. 58, 218–233 (1961).

  10. 10.

    Time-dependent processes in memory storage. Science 153, 1351–1358 (1966).

  11. 11.

    & The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171–175 (1971).

  12. 12.

    et al. Cellular networks underlying human spatial navigation. Nature 425, 184–188 (2003).

  13. 13.

    & Dynamics of the hippocampal ensemble code for space. Science 261, 1055–1058 (1993).

  14. 14.

    et al. Interactions between location and task affect the spatial and directional firing of hippocampal neurons. J. Neurosci. 15, 7079–7094 (1995).

  15. 15.

    et al. Goal-related activity in hippocampal place cells. J. Neurosci. 27, 472–482 (2007).

  16. 16.

    , , , & Accumulation of hippocampal place fields at the goal location in an annular watermaze task. J. Neurosci. 21, 1635–1644 (2001).

  17. 17.

    , , & NMDA receptors, place cells and hippocampal spatial memory. Nat. Rev. Neurosci. 5, 361–372 (2004).

  18. 18.

    The role of sleep in learning and memory. Science 294, 1048–1052 (2001).

  19. 19.

    & The contribution of sleep to hippocampus-dependent memory consolidation. Trends Cogn. Sci. 11, 442–450 (2007).

  20. 20.

    , , & Odor cues during slow-wave sleep prompt declarative memory consolidation. Science 315, 1426–1429 (2007).

  21. 21.

    Hippocampal sharp waves: their origin and significance. Brain Res. 398, 242–252 (1986).

  22. 22.

    , , & Ensemble patterns of hippocampal CA3–CA1 neurons during sharp wave–associated population events. Neuron 28, 585–594 (2000).

  23. 23.

    , , , & Fast network oscillations in the hippocampal CA1 region of the behaving rat. J. Neurosci. 19, RC20 (1999).

  24. 24.

    , , , & Selective suppression of hippocampal ripples impairs spatial memory. Nat. Neurosci. 12, 1222–1223 (2009).

  25. 25.

    & Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat. Hippocampus 20, 1–10 (2010).

  26. 26.

    , & Reactivation of hippocampal cell assemblies: effects of behavioral state, experience, and EEG dynamics. J. Neurosci. 19, 4090–4101 (1999).

  27. 27.

    & Reactivation of hippocampal ensemble memories during sleep. Science 265, 676–679 (1994).

  28. 28.

    , , , & Reactivation of experience-dependent cell assembly patterns in the hippocampus. Nat. Neurosci. 11, 209–215 (2008).

  29. 29.

    & Memory trace reactivation in hippocampal and neocortical neuronal ensembles. Curr. Opin. Neurobiol. 10, 180–186 (2000).

  30. 30.

    & Maintaining memories by reactivation. Curr. Opin. Neurobiol. 17, 698–703 (2007).

  31. 31.

    , , & Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319, 774–776 (1986).

  32. 32.

    et al. NMDA-receptor blockade by CPP impairs post-training consolidation of a rapidly acquired spatial representation in rat hippocampus. Eur. J. Neurosci. 22, 1201–1213 (2005).

  33. 33.

    & Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5. Hippocampus 9, 118–136 (1999).

  34. 34.

    , , & NMDA receptor–dependent synaptic reinforcement as a crucial process for memory consolidation. Science 290, 1170–1174 (2000).

  35. 35.

    , & Place-selective firing of CA1 pyramidal cells during sharp wave/ripple network patterns in exploratory behavior. Neuron 49, 143–155 (2006).

  36. 36.

    et al. Independent codes for spatial and episodic memory in hippocampal neuronal ensembles. Science 309, 619–623 (2005).

  37. 37.

    et al. Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade. Science 280, 2121–2126 (1998).

  38. 38.

    , , & Hippocampal CA3 output is crucial for ripple-associated reactivation and consolidation of memory. Neuron 62, 781–787 (2009).

  39. 39.

    , , , & Distinct ensemble codes in hippocampal areas CA3 and CA1. Science 305, 1295–1298 (2004).

  40. 40.

    & The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells. J. Neurosci. 7, 1951–1968 (1987).

  41. 41.

    , , & Hebbian modification of a hippocampal population pattern in the rat. J. Physiol. (Lond.) 521, 159–167 (1999).

  42. 42.

    , & Compartmentalized dendritic plasticity and input feature storage in neurons. Nature 452, 436–441 (2008).

  43. 43.

    & New experiences enhance coordinated neural activity in the hippocampus. Neuron 57, 303–313 (2008).

  44. 44.

    , , & Sequence reactivation in the hippocampus is impaired in aged rats. J. Neurosci. 28, 7883–7890 (2008).

  45. 45.

    , , , & Hippocampus leads ventral striatum in replay of place-reward information. PLoS Biol. 7, e1000173 (2009).

  46. 46.

    , , , & Replay of rule-learning related neural patterns in the prefrontal cortex during sleep. Nat. Neurosci. 12, 919–926 (2009).

  47. 47.

    & The firing of hippocampal place cells predicts the future position of freely moving rats. J. Neurosci. 9, 4101–4110 (1989).

  48. 48.

    , , & Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6, 149–172 (1996).

  49. 49.

    et al. The ventral striatum in off-line processing: ensemble reactivation during sleep and modulation by hippocampal ripples. J. Neurosci. 24, 6446–6456 (2004).

  50. 50.

    , & Methodological considerations on the use of template matching to study long-lasting memory trace replay. J. Neurosci. 26, 10727–10742 (2006).

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Acknowledgements

We thank J.N.P. Rawlins and D.M. Bannerman for discussions about the behavioral procedures; J.R. Huxter and K. Allen for discussions about data analysis and the manuscript; P. Somogyi, M. Capogna, C. Lever, O. Paulsen and T. Bienvenu for comments on a previous version of the manuscript and N. Campo-Urriza for technical assistance. This work was supported by the Medical Research Council. D.D. was successively funded by fellowships from the Institut de France-Fondation Louis D. and the International Brain Research Organization (Research Fellowship), and currently holds a Junior Research Fellowship in Neurosciences from Saint Edmund Hall College, University of Oxford.

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Affiliations

  1. MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Oxford, UK.

    • David Dupret
    • , Joseph O'Neill
    • , Barty Pleydell-Bouverie
    •  & Jozsef Csicsvari

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Contributions

D.D. conducted the experiments. D.D., J.O. and B.P.-B. analyzed data. D.D. and J.C. wrote the manuscript. J.C. 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 David Dupret or Jozsef Csicsvari.

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DOI

https://doi.org/10.1038/nn.2599

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