Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Critical role of the hippocampus in memory for sequences of events

Abstract

Recent models of hippocampal function emphasize the potential role of this brain structure in encoding and retrieving sequences of events that compose episodic memories. Here we show that hippocampal lesions produce a severe and selective impairment in the capacity of rats to remember the sequential ordering of a series of odors, despite an intact capacity to recognize odors that recently occurred. These findings support the hypothesis that hippocampal networks mediate associations between sequential events that constitute elements of an episodic memory.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Sequential order and recognition tasks.
Figure 2: Performance (mean percent correct ± s.e.m.) of control rats and rats with hippocampal lesions on sequential order memory task.
Figure 3: Performance (mean percent correct s.e.m.) of control rats and rats with hippocampal lesions on recognition for each of the different types of probes.
Figure 4: Comparison of performance on recognition and sequential order tests.
Figure 5: Hippocampal subdivisions affected by the lesions at three anterior–posterior levels.

References

  1. Vargha-Khadem, F. et al. Differential effects of early hippocampal pathology on episodic and semantic memory. Science 277, 376–380 (1997).

    Article  CAS  Google Scholar 

  2. Tulving, E. & Markowitsch, H. J. Episodic and declarative memory: role of the hippocampus. Hippocampus 8, 198–204 (1998).

    Article  CAS  Google Scholar 

  3. Mishkin, M., Suzuki, W. A., Gadian, D. G. & Vargha-Khadem, F. Hierarchical organization of cognitive memory. Phil. Trans. R. Soc. Lond. B Biol. Sci. 352, 1461–1467 (1997).

    Article  CAS  Google Scholar 

  4. Levy, W. B. A sequence predicting CA3 is a flexible associator that learns and uses context to solve hippocampal-like tasks. Hippocampus 6, 579–590 (1996).

    Article  CAS  Google Scholar 

  5. Sohal, V.S. & Hasselmo, M.E. Changes in GABAB modulation during a theta cycle may be analogous to the fall of temperature during annealing. Neural Comput. 10, 889–902 (1998).

    Article  Google Scholar 

  6. Lisman, J. E. Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate–CA3 interactions. Neuron 22, 233–242 (1999).

    Article  CAS  Google Scholar 

  7. Wallenstein, G. V., Eichenbaum, H. & Hasselmo, M. E. The hippocampus as an associator of discontiguous events. Trends Neurosci. 21, 317–323 (1998).

    Article  CAS  Google Scholar 

  8. Kesner, R. P. & Novak, J. M. Serial position curve in rats: role of the dorsal hippocampus. Science 218, 173–175 (1982).

    Article  CAS  Google Scholar 

  9. Chiba, A. A., Kesner, R. P. & Reynolds, A. M. Memory for spatial location as a function of temporal lag in rats: role of hippocampus and medial prefrontal cortex. Behav. Neural Biol. 61, 123–131 (1994).

    Article  CAS  Google Scholar 

  10. Eichenbaum, H., Dudchenko, P. A., Wood, E. R., Shapiro, M. L. & Tanila, H. The hippocampus, memory, and place cells: is it spatial memory or a memory space? Neuron 23, 209–226 (1999).

    Article  CAS  Google Scholar 

  11. Rawlins, J. N. P. Associations across time: the hippocampus as a temporary memory store. Behav. Brain Sci. 8, 479–496 (1985).

    Article  Google Scholar 

  12. Zola-Morgan, S., Squire, L. R. & Ramus, S. J. Severity of memory impairment in monkeys as a function of locus and extent of damage within the medial temporal lobe memory system. Hippocampus 4, 483–495 (1994).

    Article  CAS  Google Scholar 

  13. Murray, E. A. What have ablation studies told us about the neural substrates of stimulus memory? Semin. Neurosci. 8, 13–22 (1996).

    Article  Google Scholar 

  14. Murray, E. A. & Mishkin, M. Object recognition and location memory in monkeys with excitotoxic lesions of the amygdala and hippocampus. J. Neurosci. 18, 6568–6582 (1998).

    Article  CAS  Google Scholar 

  15. Dudchenko, P. A., Wood, E. R. & Eichenbaum, H. Neurotoxic hippocampal lesions have no effect on odor span and little effect on odor recognition memory but produce significant impairments on spatial span, recognition, and alternation. J. Neurosci. 20, 2964–2977 (2000).

    Article  CAS  Google Scholar 

  16. Aggleton, J. P. & Brown, M. W. Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. Behav. Brain Sci. 22, 425–444; discussion 444–489 (1999).

    CAS  PubMed  Google Scholar 

  17. Eichenbaum, H., Otto, T. & Cohen, N. J. Two functional components of the hippocampal memory system. Behav. Brain Sci. 17, 449–472; discussion 472–518 (1994).

    Article  Google Scholar 

  18. Brown, M. W. & Aggleton, J.P. Recognition memory: what are the roles of the perirhinal cortex and hippocampus? Nat. Rev. Neurosci. 2, 51–61 (2001).

    Article  CAS  Google Scholar 

  19. Murray, E. A. & Bussey, T. J. Perceptual-mnemonic functions of the perirhinal cortex. Trends Cogn. Sci. 3, 142–151 (1999).

    Article  CAS  Google Scholar 

  20. Gaffan, D. Dissociated effects of perirhinal cortex ablation, fornix transection and amygdalectomy: evidence for multiple memory systems in the primate temporal lobe. Exp. Brain Res. 99, 411–422 (1994).

    CAS  PubMed  Google Scholar 

  21. Mishkin, M. Memory in monkeys severely impaired by combined but not separate removal of the amygdala and hippocampus. Nature 273, 297–298 (1978).

    Article  CAS  Google Scholar 

  22. Zola, S. M. et al. Impaired recognition memory in monkeys after damage limited to the hippocampal region. J. Neurosci. 20, 451–463 (2000).

    Article  CAS  Google Scholar 

  23. Mumby, D.G. Perspectives on object-recognition memory following hippocampal damage: lessons from studies on rats. Behav. Brain Res. 127, 159–181 (2001).

    Article  CAS  Google Scholar 

  24. Gaffan, D. Scene-specific memory for objects: a model of episodic memory impairment in monkeys with fornix transection. J. Cogn. Neurosci. 6, 305–320 (1994).

    Article  CAS  Google Scholar 

  25. Clayton, N. S. & Dickinson, A. Episodic-like memory during cache recovery by scrub jays. Nature 395, 272–274 (1998).

    Article  CAS  Google Scholar 

  26. Treves, A. & Rolls, E. T. Computational analysis of the role of the hippocampus in memory. Hippocampus 4, 374–391 (1994).

    Article  CAS  Google Scholar 

  27. Kesner, R. P. in Neurobiology of Comparative Cognition (eds. Kesner, R. P. & Olton, D. S.) 179–204 (Lawrence Erlbaum, Mahwah, New Jersey, 1990).

    Google Scholar 

  28. Shapiro, M. L. & Olton, D. S. in Memory Systems (eds. Schacter, D. L. & Tulving, E.) 87–117 (MIT Press, Cambridge, Massachusetts, 1994).

    Google Scholar 

  29. Bunsey, M. & Eichenbaum, H. Conservation of hippocampal memory function in rats and humans. Nature 379, 255–257 (1996).

    Article  CAS  Google Scholar 

  30. Dusek, J. A. & Eichenbaum, H. The hippocampus and memory for orderly stimulus relations. Proc. Natl. Acad. Sci. USA 94, 7109–7114 (1997).

    Article  CAS  Google Scholar 

  31. Jarrard, L. E. in The Hippocampus Vol. 4 (eds. Isaacson, R. L. & Pribram, K. H.) 93–126 (Plenum, New York, 1986).

    Book  Google Scholar 

  32. Swanson, L. W. Brain Maps: Structure of the Rat Brain Slides 32, 37 & 39 (Elsevier, Amsterdam, 1992).

    Google Scholar 

Download references

Acknowledgements

We thank S. Rubin, J. Tourigny, S. Wright, L. Griffith, A. Cahill and A. Ceriales for help with behavioral testing and histological work. Supported by NIMH MH52090 (H.B.E.), NIA AG09973 (H.B.E.), and NSERC (N.J.F.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Howard B. Eichenbaum.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fortin, N., Agster, K. & Eichenbaum, H. Critical role of the hippocampus in memory for sequences of events. Nat Neurosci 5, 458–462 (2002). https://doi.org/10.1038/nn834

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn834

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing