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Potential role for adult neurogenesis in the encoding of time in new memories

Abstract

The dentate gyrus in the hippocampus is one of two brain regions with lifelong neurogenesis in mammals. Despite an increasing amount of information about the characteristics of the newborn granule cells, the specific contribution of their robust generation to memory formation by the hippocampus remains unclear. We describe here a possible role that this population of young granule cells may have in the formation of temporal associations in memory. Neurogenesis is a continuous process; the newborn population is only composed of the same cells for a short period of time. As time passes, the young neurons mature or die and others are born, gradually changing the identity of this young population. We discuss the possibility that one cognitive impact of this gradually changing population on hippocampal memory formation is the formation of the temporal clusters of long-term episodic memories seen in some human psychological studies.

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Figure 1: Growth and maturation of adult newborn granule cells.
Figure 2: Schematic showing how newborn granule cells may encode temporal memories in the hippocampus.
Figure 3: Cartoon example of how temporal associations may exist in long-term human memories.

References

  1. Ming, G.L. & Song, H. Adult neurogenesis in the mammalian central nervous system. Annu. Rev. Neurosci. 28, 223–250 (2005).

    Article  CAS  Google Scholar 

  2. Gage, F.H. Neurogenesis in the adult brain. J. Neurosci. 22, 612–613 (2002).

    Article  CAS  Google Scholar 

  3. Altman, J. & Bayer, S.A. Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J. Comp. Neurol. 301, 365–381 (1990).

    Article  CAS  Google Scholar 

  4. Eriksson, P.S. et al. Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313–1317 (1998).

    Article  CAS  Google Scholar 

  5. van Praag, H., Kempermann, G. & Gage, F.H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2, 266–270 (1999).

    Article  CAS  Google Scholar 

  6. Gould, E., Beylin, A., Tanapat, P., Reeves, A. & Shors, T.J. Learning enhances adult neurogenesis in the hippocampal formation. Nat. Neurosci. 2, 260–265 (1999).

    Article  CAS  Google Scholar 

  7. Kempermann, G., Kuhn, H.G. & Gage, F.H. More hippocampal neurons in adult mice living in an enriched environment. Nature 386, 493–495 (1997).

    Article  CAS  PubMed Central  Google Scholar 

  8. Leuner, B., Gould, E. & Shors, T.J. Is there a link between adult neurogenesis and learning? Hippocampus 16, 216–224 (2006).

    Article  Google Scholar 

  9. Schmidt-Hieber, C., Jonas, P. & Bischofberger, J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429, 184–187 (2004).

    Article  CAS  Google Scholar 

  10. van Praag, H. et al. Functional neurogenesis in the adult hippocampus. Nature 415, 1030–1034 (2002).

    Article  CAS  PubMed Central  Google Scholar 

  11. Kempermann, G., Wiskott, L. & Gage, F.H. Functional significance of adult neurogenesis. Curr. Opin. Neurobiol. 14, 186–191 (2004).

    Article  CAS  Google Scholar 

  12. Squire, L.R., Stark, C.E. & Clark, R.E. The medial temporal lobe. Annu. Rev. Neurosci. 27, 279–306 (2004).

    Article  CAS  PubMed Central  Google Scholar 

  13. McNaughton, B.L. & Morris, R.G. Hippocampal synaptic enhancement and information storage within a distributed memory system. Trends Neurosci. 10, 408–415 (1987).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Hasselmo, M.E., Wyble, B.P. & Wallenstein, G.V. Encoding and retrieval of episodic memories: role of cholinergic and GABAergic modulation in the hippocampus. Hippocampus 6, 693–708 (1996).

    Article  CAS  Google Scholar 

  16. Henze, D.A., Wittner, L. & Buzsaki, G. Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo. Nat. Neurosci. 5, 790–795 (2002).

    Article  CAS  Google Scholar 

  17. Amaral, D.G., Ishizuka, N. & Claiborne, B. Neurons, numbers and the hippocampal network. Prog. Brain Res. 83, 1–11 (1990).

    Article  CAS  PubMed Central  Google Scholar 

  18. Jung, M.W. & McNaughton, B.L. Spatial selectivity of unit activity in the hippocampal granular layer. Hippocampus 3, 165–182 (1993).

    Article  CAS  PubMed Central  Google Scholar 

  19. Chawla, M.K. et al. Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience. Hippocampus 15, 579–586 (2005).

    Article  CAS  Google Scholar 

  20. Treves, A. & Rolls, E.T. Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network. Hippocampus 2, 189–199 (1992).

    Article  CAS  PubMed Central  Google Scholar 

  21. Kobayashi, K. & Poo, M.M. Spike train timing-dependent associative modification of hippocampal CA3 recurrent synapses by mossy fibers. Neuron 41, 445–454 (2004).

    Article  CAS  PubMed Central  Google Scholar 

  22. McMahon, D.B. & Barrionuevo, G. Short- and long-term plasticity of the perforant path synapse in hippocampal area CA3. J. Neurophysiol. 88, 528–533 (2002).

    Article  PubMed Central  Google Scholar 

  23. Kesner, R.P., Lee, I. & Gilbert, P. A behavioral assessment of hippocampal function based on a subregional analysis. Rev. Neurosci. 15, 333–351 (2004).

    Article  PubMed Central  Google Scholar 

  24. Lee, I. & Kesner, R.P. Encoding versus retrieval of spatial memory: double dissociation between the dentate gyrus and the perforant path inputs into CA3 in the dorsal hippocampus. Hippocampus 14, 66–76 (2004).

    Article  PubMed Central  Google Scholar 

  25. Shors, T.J., Townsend, D.A., Zhao, M., Kozorovitskiy, Y. & Gould, E. Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 12, 578–584 (2002).

    Article  PubMed Central  Google Scholar 

  26. Wiskott, L., Rasch, M.J. & Kempermann, G. A functional hypothesis for adult hippocampal neurogenesis: avoidance of catastrophic interference in the dentate gyrus. Hippocampus 16, 329–343 (2006).

    Article  PubMed Central  Google Scholar 

  27. Becker, S. A computational principle for hippocampal learning and neurogenesis. Hippocampus 15, 722–738 (2005).

    Article  PubMed Central  Google Scholar 

  28. Schinder, A.F. & Gage, F.H. A hypothesis about the role of adult neurogenesis in hippocampal function. Physiology (Bethesda) 19, 253–261 (2004).

    Google Scholar 

  29. Hastings, N.B. & Gould, E. Rapid extension of axons into the CA3 region by adult-generated granule cells. J. Comp. Neurol. 413, 146–154 (1999).

    Article  CAS  PubMed Central  Google Scholar 

  30. Zhao, C., Teng, E.M., Summers, R.G., Ming, G.L. & Gage, F.H. Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J. Neurosci. 26, 3–11 (2006).

    Article  CAS  Google Scholar 

  31. Esposito, M.S. et al. Neuronal differentiation in the adult hippocampus recapitulates embryonic development. J. Neurosci. 25, 10074–10086 (2005).

    Article  CAS  Google Scholar 

  32. Song, H. et al. New neurons in the adult mammalian brain: synaptogenesis and functional integration. J. Neurosci. 25, 10366–10368 (2005).

    Article  CAS  Google Scholar 

  33. Kempermann, G., Jessberger, S., Steiner, B. & Kronenberg, G. Milestones of neuronal development in the adult hippocampus. Trends Neurosci. 27, 447–452 (2004).

    Article  CAS  Google Scholar 

  34. Aristotle. On memory. in The Complete Works of Artistotle (ed. Barnes, J.) 714–720 (Princeton Univ. Press, Princeton, New Jersey, 1984).

  35. Friedman, W.J. Memory for the time of past events. Psychol. Bull. 113, 44–66 (1993).

    Article  Google Scholar 

  36. Loftus, E.F. & Marburger, W. Since the eruption of Mt. St. Helens, has anyone beaten you up? Improving the accuracy of retrospective reports with landmark events. Mem. Cognit. 11, 114–120 (1983).

    Article  CAS  Google Scholar 

  37. Shum, M.S. The role of temporal landmarks in autobiographical memory process. Psychol. Bull. 124, 423–442 (1998).

    Article  CAS  Google Scholar 

  38. Brown, N.R. & Schopflocher, D. Event cueing, event clusters, and the temporal distribution of autobiographical memories. Appl. Cogn. Psychol. 12, 305–319 (1998).

    Article  Google Scholar 

  39. Burt, C.D.B., Kemp, S. & Conway, M.A. Themes, events, and episodes in autobiographical memory. Mem. Cognit. 31, 317–325 (2003).

    Article  Google Scholar 

  40. Frankland, P.W. & Bontempi, B. The organization of recent and remote memories. Nat. Rev. Neurosci. 6, 119–130 (2005).

    Article  CAS  Google Scholar 

  41. Zola-Morgan, S., Squire, L.R. & Amaral, D.G. Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J. Neurosci. 6, 2950–2967 (1986).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  43. Bayley, P.J., Gold, J.J., Hopkins, R.O. & Squire, L.R. The neuroanatomy of remote memory. Neuron 46, 799–810 (2005).

    Article  CAS  PubMed Central  Google Scholar 

  44. Wiltgen, B.J., Brown, R.A., Talton, L.E. & Silva, A.J. New circuits for old memories: the role of the neocortex in consolidation. Neuron 44, 101–108 (2004).

    Article  CAS  Google Scholar 

  45. Kuhn, H.G., Dickinson-Anson, H. & Gage, F.H. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J. Neurosci. 16, 2027–2033 (1996).

    Article  CAS  Google Scholar 

  46. Nixon, K. & Crews, F.T. Binge ethanol exposure decreases neurogenesis in adult rat hippocampus. J. Neurochem. 83, 1087–1093 (2002).

    Article  CAS  Google Scholar 

  47. Malberg, J.E., Eisch, A.J., Nestler, E.J. & Duman, R.S. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci. 20, 9104–9110 (2000).

    Article  CAS  Google Scholar 

  48. White, A.M., Matthews, D.B. & Best, P.J. Ethanol, memory, and hippocampal function: a review of recent findings. Hippocampus 10, 88–93 (2000).

    Article  CAS  Google Scholar 

  49. Austin, M.P., Mitchell, P. & Goodwin, G.M. Cognitive deficits in depression: possible implications for functional neuropathology. Br. J. Psychiatry 178, 200–206 (2001).

    Article  CAS  Google Scholar 

  50. Erickson, C.A. & Barnes, C.A. The neurobiology of memory changes in normal aging. Exp. Gerontol. 38, 61–69 (2003).

    Article  CAS  PubMed Central  Google Scholar 

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Acknowledgements

We thank J. Elman, T. Sejnowski, L. Squire and C. Stevens for useful discussion and comments, M.L. Gage for editorial comments, and J. Simon for assistance with figures. This work was funded in part by the Kavli Institute for Brain and Mind, the Lookout Fund, the Defense Advanced Research Projects Agency (DARPA), the US National Institutes of Health (NS-05050217 and NS-05052842) and National Institute of Aging (AG-020938).

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Correspondence to Fred H Gage.

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Aimone, J., Wiles, J. & Gage, F. Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9, 723–727 (2006). https://doi.org/10.1038/nn1707

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