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The reorganization and reactivation of hippocampal maps predict spatial memory performance

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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Figure 1: Daily learning of a new set of goal locations on the cheeseboard maze.
Figure 2: Goal-related reorganization of hippocampal assembly patterns.
Figure 3: Locating rewards during the Cued version of the cheeseboard maze task.
Figure 4: eSWR-associated activity of CA1 place cells.
Figure 5: Reactivation of CA1 place-related assembly patterns.

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References

  1. O'Keefe, J. & Nadel, L. The Hippocampus as a Cognitive Map (Oxford Univ. Press, 1978).

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Hebb, D.O. The Organization of Behavior (Wiley, New York, 1949).

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

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. McClelland, J.L., McNaughton, B.L. & O'Reilly, R.C. 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).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Wilson, M.A. & McNaughton, B.L. Dynamics of the hippocampal ensemble code for space. Science 261, 1055–1058 (1993).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hollup, S.A., Molden, S., Donnett, J.G., Moser, M.B. & Moser, E.I. Accumulation of hippocampal place fields at the goal location in an annular watermaze task. J. Neurosci. 21, 1635–1644 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nakazawa, K., McHugh, T.J., Wilson, M.A. & Tonegawa, S. NMDA receptors, place cells and hippocampal spatial memory. Nat. Rev. Neurosci. 5, 361–372 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  20. Rasch, B., Buchel, C., Gais, S. & Born, J. Odor cues during slow-wave sleep prompt declarative memory consolidation. Science 315, 1426–1429 (2007).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  22. Csicsvari, J., Hirase, H., Mamiya, A. & Buzsaki, G. Ensemble patterns of hippocampal CA3–CA1 neurons during sharp wave–associated population events. Neuron 28, 585–594 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Csicsvari, J., Hirase, H., Czurko, A., Mamiya, A. & Buzsaki, G. Fast network oscillations in the hippocampal CA1 region of the behaving rat. J. Neurosci. 19, RC20 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Girardeau, G., Benchenane, K., Wiener, S.I., Buzsaki, G. & Zugaro, M.B. Selective suppression of hippocampal ripples impairs spatial memory. Nat. Neurosci. 12, 1222–1223 (2009).

    Article  CAS  PubMed  Google Scholar 

  25. Ego-Stengel, V. & Wilson, M.A. Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat. Hippocampus 20, 1–10 (2010).

    PubMed  PubMed Central  Google Scholar 

  26. Kudrimoti, H.S., Barnes, C.A. & McNaughton, B.L. Reactivation of hippocampal cell assemblies: effects of behavioral state, experience, and EEG dynamics. J. Neurosci. 19, 4090–4101 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wilson, M.A. & McNaughton, B.L. Reactivation of hippocampal ensemble memories during sleep. Science 265, 676–679 (1994).

    Article  CAS  PubMed  Google Scholar 

  28. O'Neill, J., Senior, T.J., Allen, K., Huxter, J.R. & Csicsvari, J. Reactivation of experience-dependent cell assembly patterns in the hippocampus. Nat. Neurosci. 11, 209–215 (2008).

    Article  CAS  PubMed  Google Scholar 

  29. Sutherland, G.R. & McNaughton, B. Memory trace reactivation in hippocampal and neocortical neuronal ensembles. Curr. Opin. Neurobiol. 10, 180–186 (2000).

    Article  CAS  PubMed  Google Scholar 

  30. Rasch, B. & Born, J. Maintaining memories by reactivation. Curr. Opin. Neurobiol. 17, 698–703 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. Morris, R.G., Anderson, E., Lynch, G.S. & Baudry, M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319, 774–776 (1986).

    Article  CAS  PubMed  Google Scholar 

  32. McDonald, R.J. 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).

    Article  PubMed  Google Scholar 

  33. Steele, R.J. & Morris, R.G. 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).

    Article  CAS  PubMed  Google Scholar 

  34. Shimizu, E., Tang, Y.P., Rampon, C. & Tsien, J.Z. NMDA receptor–dependent synaptic reinforcement as a crucial process for memory consolidation. Science 290, 1170–1174 (2000).

    Article  CAS  PubMed  Google Scholar 

  35. O'Neill, J., Senior, T. & Csicsvari, J. Place-selective firing of CA1 pyramidal cells during sharp wave/ripple network patterns in exploratory behavior. Neuron 49, 143–155 (2006).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  38. Nakashiba, T., Buhl, D.L., McHugh, T.J. & Tonegawa, S. Hippocampal CA3 output is crucial for ripple-associated reactivation and consolidation of memory. Neuron 62, 781–787 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Leutgeb, S., Leutgeb, J.K., Treves, A., Moser, M.B. & Moser, E.I. Distinct ensemble codes in hippocampal areas CA3 and CA1. Science 305, 1295–1298 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. King, C., Henze, D.A., Leinekugel, X. & Buzsaki, G. Hebbian modification of a hippocampal population pattern in the rat. J. Physiol. (Lond.) 521, 159–167 (1999).

    Article  CAS  Google Scholar 

  42. Losonczy, A., Makara, J.K. & Magee, J.C. Compartmentalized dendritic plasticity and input feature storage in neurons. Nature 452, 436–441 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. Cheng, S. & Frank, L.M. New experiences enhance coordinated neural activity in the hippocampus. Neuron 57, 303–313 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gerrard, J.L., Burke, S.N., McNaughton, B.L. & Barnes, C.A. Sequence reactivation in the hippocampus is impaired in aged rats. J. Neurosci. 28, 7883–7890 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lansink, C.S., Goltstein, P.M., Lankelma, J.V., McNaughton, B.L. & Pennartz, C.M. Hippocampus leads ventral striatum in replay of place-reward information. PLoS Biol. 7, e1000173 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Peyrache, A., Khamassi, M., Benchenane, K., Wiener, S.I. & Battaglia, F.P. Replay of rule-learning related neural patterns in the prefrontal cortex during sleep. Nat. Neurosci. 12, 919–926 (2009).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Skaggs, W.E., McNaughton, B.L., Wilson, M.A. & Barnes, C.A. Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6, 149–172 (1996).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Tatsuno, M., Lipa, P. & McNaughton, B.L. Methodological considerations on the use of template matching to study long-lasting memory trace replay. J. Neurosci. 26, 10727–10742 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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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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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.

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Correspondence to David Dupret or Jozsef Csicsvari.

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The authors declare no competing financial interests.

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Dupret, D., O'Neill, J., Pleydell-Bouverie, B. et al. The reorganization and reactivation of hippocampal maps predict spatial memory performance. Nat Neurosci 13, 995–1002 (2010). https://doi.org/10.1038/nn.2599

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