New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? (original) (raw)

References

  1. Altman, J. & Das, G. D. Post-natal origin of microneurones in the rat brain. Nature 207, 953–956 (1965).
    CAS PubMed Google Scholar
  2. Gage, F. H. Mammalian neural stem cells. Science 287, 1433–1438 (2000).
    CAS PubMed Google Scholar
  3. Enikolopov, G. & Overstreet Wadiche, L. in Adult Neurogenesis (eds. Gage, F. H., Kempermann, G. & Song, H.) 81–100 (Cold Spring Harbor Laboratory Press, New York, 2008).
    Google Scholar
  4. Kuhn, H. G. & Peterson, D. A. in Adult Neurogenesis (eds. Gage, F. H., Kempermann, G. & Song, H.) 25–47 (Cold Spring Harbor Laboratory Press, New York, 2008).
    Google Scholar
  5. Zhao, C. in Adult Neurogenesis (eds. Gage, F. H., Kempermann, G. & Song, H.) 101–117 (Cold Spring Harbor Laboratory Press, New York, 2008).
    Google Scholar
  6. Zhao, C., Deng, W. & Gage, F. H. Mechanisms and functional implications of adult neurogenesis. Cell 132, 645–660 (2008).
    CAS PubMed Google Scholar
  7. Suh, H., Deng, W. & Gage, F. H. Signaling in adult neurogenesis. Annu. Rev. Cell Dev. Biol. 25, 253–275 (2009).
    CAS PubMed Google Scholar
  8. Grubb, M. S., Nissant, A., Murray, K. & Lledo, P. M. Functional maturation of the first synapse in olfaction: development and adult neurogenesis. J. Neurosci. 28, 2919–2932 (2008).
    CAS PubMed PubMed Central Google Scholar
  9. Nissant, A., Bardy, C., Katagiri, H., Murray, K. & Lledo, P. M. Adult neurogenesis promotes synaptic plasticity in the olfactory bulb. Nature Neurosci. 12, 728–730 (2009).
    CAS PubMed Google Scholar
  10. Breton-Provencher, V., Lemasson, M., Peralta, M. R. III & Saghatelyan, A. Interneurons produced in adulthood are required for the normal functioning of the olfactory bulb network and for the execution of selected olfactory behaviors. J. Neurosci. 29, 15245–15257 (2009).
    CAS PubMed PubMed Central Google Scholar
  11. Whitman, M. C. & Greer, C. A. Adult neurogenesis and the olfactory system. Prog. Neurobiol. 89, 162–175 (2009).
    PubMed PubMed Central Google Scholar
  12. Squire, L. R. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol. Rev. 99, 195–231 (1992).
    CAS PubMed Google Scholar
  13. Sahay, A. & Hen, R. Hippocampal neurogenesis and depression. Novartis Found. Symp. 289, 152–160; discussion 160–164, 193–195 (2008).
    CAS PubMed Google Scholar
  14. David, D. J. et al. Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron 62, 479–493 (2009).
    CAS PubMed PubMed Central Google Scholar
  15. Cameron, H. A., Woolley, C. S., McEwen, B. S. & Gould, E. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56, 337–344 (1993).
    CAS PubMed Google Scholar
  16. Zhao, C., Teng, E. M., Summers, R. G. Jr, 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).
    CAS PubMed PubMed Central Google Scholar
  17. Snyder, J. S. et al. Adult-born hippocampal neurons are more numerous, faster maturing, and more involved in behavior in rats than in mice. J. Neurosci. 29, 14484–14495 (2009).
    CAS PubMed PubMed Central Google Scholar
  18. Esposito, M. S. et al. Neuronal differentiation in the adult hippocampus recapitulates embryonic development. J. Neurosci. 25, 10074–10086 (2005). The first systematic characterization of the process of adult hippocampal neurogenesis regarding the morphological and physiological maturation of adult-born DGCs.
    CAS PubMed PubMed Central Google Scholar
  19. Ge, S. et al. GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439, 589–593 (2006).
    CAS PubMed Google Scholar
  20. Hastings, N. B., Seth, M. I., Tanapat, P., Rydel, T. A. & Gould, E. Granule neurons generated during development extend divergent axon collaterals to hippocampal area CA3. J. Comp. Neurol. 452, 324–333 (2002).
    PubMed Google Scholar
  21. Overstreet Wadiche, L., Bromberg, D. A., Bensen, A. L. & Westbrook, G. L. GABAergic signaling to newborn neurons in dentate gyrus. J. Neurophysiol. 94, 4528–4532 (2005).
    PubMed Google Scholar
  22. Markwardt, S. J., Wadiche, J. I. & Overstreet-Wadiche, L. S. Input-specific GABAergic signaling to newborn neurons in adult dentate gyrus. J. Neurosci. 29, 15063–15072 (2009).
    CAS PubMed PubMed Central Google Scholar
  23. Jagasia, R. et al. GABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus. J. Neurosci. 29, 7966–7977 (2009).
    CAS PubMed PubMed Central Google Scholar
  24. Toni, N. et al. Synapse formation on neurons born in the adult hippocampus. Nature Neurosci. 10, 727–734 (2007).
    CAS PubMed Google Scholar
  25. Toni, N. et al. Neurons born in the adult dentate gyrus form functional synapses with target cells. Nature Neurosci. 11, 901–907 (2008).
    CAS PubMed Google Scholar
  26. Faulkner, R. L. et al. Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain. Proc. Natl Acad. Sci. USA 105, 14157–14162 (2008).
    CAS PubMed PubMed Central Google Scholar
  27. Bliss, T. V. & Collingridge, G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 (1993).
    CAS PubMed Google Scholar
  28. Tashiro, A., Sandler, V. M., Toni, N., Zhao, C. & Gage, F. H. NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus. Nature 442, 929–933 (2006).
    CAS PubMed Google Scholar
  29. Ge, S., Yang, C. H., Hsu, K. S., Ming, G. L. & Song, H. A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54, 559–566 (2007). This study demonstrated the enhanced plasticity of developing adult-born DGCs by a systematic characterization of retrovirus-labelled DGCs at different time points.
    CAS PubMed PubMed Central Google Scholar
  30. Schmidt-Hieber, C., Jonas, P. & Bischofberger, J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429, 184–187 (2004).
    CAS PubMed Google Scholar
  31. Ambrogini, P. et al. Morpho-functional characterization of neuronal cells at different stages of maturation in granule cell layer of adult rat dentate gyrus. Brain Res. 1017, 21–31 (2004).
    CAS PubMed Google Scholar
  32. Scobie, K. N. et al. Kruppel-like factor 9 is necessary for late-phase neuronal maturation in the developing dentate gyrus and during adult hippocampal neurogenesis. J. Neurosci. 29, 9875–9887 (2009).
    CAS PubMed PubMed Central Google Scholar
  33. Gould, E., Beylin, A., Tanapat, P., Reeves, A. & Shors, T. J. Learning enhances adult neurogenesis in the hippocampal formation. Nature Neurosci. 2, 260–265 (1999).
    CAS PubMed Google Scholar
  34. Epp, J. R., Spritzer, M. D. & Galea, L. A. Hippocampus-dependent learning promotes survival of new neurons in the dentate gyrus at a specific time during cell maturation. Neuroscience 149, 273–285 (2007).
    CAS PubMed Google Scholar
  35. Leuner, B. et al. Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J. Neurosci. 24, 7477–7481 (2004).
    CAS PubMed PubMed Central Google Scholar
  36. Leuner, B., Waddell, J., Gould, E. & Shors, T. J. Temporal discontiguity is neither necessary nor sufficient for learning-induced effects on adult neurogenesis. J. Neurosci. 26, 13437–13442 (2006).
    CAS PubMed PubMed Central Google Scholar
  37. Dupret, D. et al. Spatial learning depends on both the addition and removal of new hippocampal neurons. PLoS Biol. 5, e214 (2007).
    PubMed PubMed Central Google Scholar
  38. Dobrossy, M. D. et al. Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date. Mol. Psychiatry 8, 974–982 (2003).
    CAS PubMed Google Scholar
  39. van Praag, H., Kempermann, G. & Gage, F. H. Neural consequences of environmental enrichment. Nature Rev. Neurosci. 1, 191–198 (2000).
    CAS Google Scholar
  40. Kempermann, G., Kuhn, H. G. & Gage, F. H. More hippocampal neurons in adult mice living in an enriched environment. Nature 386, 493–495 (1997). The first study to show the regulation of the survival of adult-born DGCs by experience in mice.
    CAS PubMed Google Scholar
  41. Tashiro, A., Makino, H. & Gage, F. H. Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. J. Neurosci. 27, 3252–3259 (2007). The authors showed that the experiences of mice when the adult-born DGCs are in a hyper-excitable stage affect the subsequent responsiveness of these DGCs to various inputs.
    CAS PubMed PubMed Central Google Scholar
  42. Bruel-Jungerman, E., Laroche, S. & Rampon, C. New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment. Eur. J. Neurosci. 21, 513–521 (2005).
    PubMed Google Scholar
  43. Meshi, D. et al. Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment. Nature Neurosci. 9, 729–731 (2006).
    CAS PubMed Google Scholar
  44. Hillman, C. H., Erickson, K. I. & Kramer, A. F. Be smart, exercise your heart: exercise effects on brain and cognition. Nature Rev. Neurosci. 9, 58–65 (2008).
    CAS Google Scholar
  45. van Praag, H. Exercise and the brain: something to chew on. Trends Neurosci. 32, 283–290 (2009).
    CAS PubMed PubMed Central Google Scholar
  46. van Praag, H., Kempermann, G. & Gage, F. H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature Neurosci. 2, 266–270 (1999).
    CAS PubMed Google Scholar
  47. van Praag, H., Shubert, T., Zhao, C. & Gage, F. H. Exercise enhances learning and hippocampal neurogenesis in aged mice. J. Neurosci. 25, 8680–8685 (2005).
    CAS PubMed PubMed Central Google Scholar
  48. Muotri, A. R., Zhao, C., Marchetto, M. C. & Gage, F. H. Environmental influence on L1 retrotransposons in the adult hippocampus. Hippocampus 19, 1002–1007 (2009).
    CAS PubMed PubMed Central Google Scholar
  49. Snyder, J. S., Glover, L. R., Sanzone, K. M., Kamhi, J. F. & Cameron, H. A. The effects of exercise and stress on the survival and maturation of adult-generated granule cells. Hippocampus 19, 898–906 (2009).
    CAS PubMed PubMed Central Google Scholar
  50. van Praag, H., Christie, B. R., Sejnowski, T. J. & Gage, F. H. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc. Natl Acad. Sci. USA 96, 13427–13431 (1999).
    CAS PubMed PubMed Central Google Scholar
  51. Leasure, J. L. & Decker, L. Social isolation prevents exercise-induced proliferation of hippocampal progenitor cells in female rats. Hippocampus 19, 907–912 (2009).
    PubMed Google Scholar
  52. Bruel-Jungerman, E., Davis, S., Rampon, C. & Laroche, S. Long-term potentiation enhances neurogenesis in the adult dentate gyrus. J. Neurosci. 26, 5888–5893 (2006).
    CAS PubMed PubMed Central Google Scholar
  53. Chun, S. K., Sun, W., Park, J. J. & Jung, M. W. Enhanced proliferation of progenitor cells following long-term potentiation induction in the rat dentate gyrus. Neurobiol. Learn. Mem. 86, 322–329 (2006).
    PubMed Google Scholar
  54. Madsen, T. M., Greisen, M. H., Nielsen, S. M., Bolwig, T. G. & Mikkelsen, J. D. Electroconvulsive stimuli enhance both neuropeptide Y receptor Y1 and Y2 messenger RNA expression and levels of binding in the rat hippocampus. Neuroscience 98, 33–39 (2000).
    CAS PubMed Google Scholar
  55. 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).
    CAS PubMed PubMed Central Google Scholar
  56. Parent, J. M. et al. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J. Neurosci. 17, 3727–3738 (1997).
    CAS PubMed PubMed Central Google Scholar
  57. Jessberger, S. et al. Seizure-associated, aberrant neurogenesis in adult rats characterized with retrovirus-mediated cell labeling. J. Neurosci. 27, 9400–9407 (2007).
    CAS PubMed PubMed Central Google Scholar
  58. Parent, J. M., Elliott, R. C., Pleasure, S. J., Barbaro, N. M. & Lowenstein, D. H. Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Ann. Neurol. 59, 81–91 (2006).
    PubMed Google Scholar
  59. Overstreet-Wadiche, L. S., Bromberg, D. A., Bensen, A. L. & Westbrook, G. L. Seizures accelerate functional integration of adult-generated granule cells. J. Neurosci. 26, 4095–4103 (2006).
    CAS PubMed PubMed Central Google Scholar
  60. Guzowski, J. F. et al. Mapping behaviorally relevant neural circuits with immediate-early gene expression. Curr. Opin. Neurobiol. 15, 599–606 (2005).
    CAS PubMed Google Scholar
  61. Jessberger, S. & Kempermann, G. Adult-born hippocampal neurons mature into activity-dependent responsiveness. Eur. J. Neurosci. 18, 2707–2712 (2003).
    PubMed Google Scholar
  62. Ramirez-Amaya, V., Marrone, D. F., Gage, F. H., Worley, P. F. & Barnes, C. A. Integration of new neurons into functional neural networks. J. Neurosci. 26, 12237–12241 (2006).
    CAS PubMed PubMed Central Google Scholar
  63. Kee, N., Teixeira, C. M., Wang, A. H. & Frankland, P. W. Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nature Neurosci. 10, 355–362 (2007).
    CAS PubMed Google Scholar
  64. Trouche, S., Bontempi, B., Roullet, P. & Rampon, C. Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory. Proc. Natl Acad. Sci. USA 106, 5919–5924 (2009).
    CAS PubMed PubMed Central Google Scholar
  65. Gould, E., Tanapat, P., Hastings, N. B. & Shors, T. J. Neurogenesis in adulthood: a possible role in learning. Trends Cogn. Sci. 3, 186–192 (1999).
    CAS PubMed Google Scholar
  66. Kempermann, G., Wiskott, L. & Gage, F. H. Functional significance of adult neurogenesis. Curr. Opin. Neurobiol. 14, 186–191 (2004).
    CAS PubMed Google Scholar
  67. 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
  68. Marr, D. Simple memory: a theory for archicortex. Philos. Trans. R. Soc. Lond. B Biol. Sci. 262, 23–81 (1971).
    CAS PubMed Google Scholar
  69. McNaughton, B. L. & Morris, R. G. M. Hippocampal synaptic enhancement and information storage within a distributed memory system. Trends Neurosci. 10, 408–415 (1987).
    Google Scholar
  70. O'Reilly, R. C. & McClelland, J. L. Hippocampal conjunctive encoding, storage, and recall: avoiding a trade-off. Hippocampus 4, 661–682 (1994).
    CAS PubMed Google Scholar
  71. Rolls, E. T. A theory of hippocampal function in memory. Hippocampus 6, 601–620 (1996).
    CAS PubMed Google Scholar
  72. 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).
    CAS PubMed Google Scholar
  73. Bakker, A., Kirwan, C. B., Miller, M. & Stark, C. E. Pattern separation in the human hippocampal CA3 and dentate gyrus. Science 319, 1640–1642 (2008).
    CAS PubMed PubMed Central Google Scholar
  74. Leutgeb, J. K., Leutgeb, S., Moser, M. B. & Moser, E. I. Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science 315, 961–966 (2007).
    CAS PubMed Google Scholar
  75. McHugh, T. J. et al. Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science 317, 94–99 (2007).
    CAS PubMed Google Scholar
  76. Aimone, J. B. & Wiskott, L. in Adult Neurogenesis (eds. Gage, F. H., Kempermann, G. & Song, H.) 101–117 (Cold Spring Harbor Laboratory Press, New York, 2008).
    Google Scholar
  77. Chambers, R. A., Potenza, M. N., Hoffman, R. E. & Miranker, W. Simulated apoptosis/neurogenesis regulates learning and memory capabilities of adaptive neural networks. Neuropsychopharmacology 29, 747–758 (2004).
    PubMed Google Scholar
  78. Deisseroth, K. et al. Excitation-neurogenesis coupling in adult neural stem/progenitor cells. Neuron 42, 535–552 (2004).
    CAS PubMed Google Scholar
  79. Crick, C. & Miranker, W. Apoptosis, neurogenesis, and information content in Hebbian networks. Biol. Cybern. 94, 9–19 (2006).
    PubMed Google Scholar
  80. Becker, S. A computational principle for hippocampal learning and neurogenesis. Hippocampus 15, 722–738 (2005).
    PubMed Google Scholar
  81. 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).
    PubMed Google Scholar
  82. Weisz, V. I. & Argibay, P. F. A putative role for neurogenesis in neuro-computational terms: inferences from a hippocampal model. Cognition 112, 229–240 (2009).
    PubMed Google Scholar
  83. Aimone, J. B., Wiles, J. & Gage, F. H. Computational influence of adult neurogenesis on memory encoding. Neuron 61, 187–202 (2009). A bottom-up computational model of adult hippocampal neurogenesis. The authors proposed a role for adult-born DGCs with enhanced excitability in pattern integration through their broad tuning properties.
    CAS PubMed PubMed Central Google Scholar
  84. Aimone, J. B., Wiles, J. & Gage, F. H. Potential role for adult neurogenesis in the encoding of time in new memories. Nature Neurosci. 9, 723–727 (2006).
    CAS PubMed Google Scholar
  85. Friedman, W. J. Comment on “Potential role for adult neurogenesis in the encoding of time in new memories”. Hippocampus 17, 503–504 (2007).
    PubMed Google Scholar
  86. Becker, S. & Wojtowicz, J. M. A model of hippocampal neurogenesis in memory and mood disorders. Trends Cogn. Sci. 11, 70–76 (2007).
    PubMed Google Scholar
  87. Dupret, D. et al. Spatial relational memory requires hippocampal adult neurogenesis. PLoS One 3, e1959 (2008).
    PubMed PubMed Central Google Scholar
  88. Saxe, M. D. et al. Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc. Natl Acad. Sci. USA 103, 17501–17506 (2006).
    CAS PubMed PubMed Central Google Scholar
  89. Shors, T. J. et al. Neurogenesis in the adult is involved in the formation of trace memories. Nature 410, 372–376 (2001). The first study to show the functional importance of adult neurogenesis. The authors discovered that rats with reduced adult neurogenesis were impaired in learning conditioned response in an eye blink trace conditioning paradigm.
    CAS PubMed Google Scholar
  90. 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).
    PubMed PubMed Central Google Scholar
  91. Clelland, C. D. et al. A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325, 210–213 (2009). The first study to suggest an involvement of adult hippocampal neurogenesis in pattern separation, a proposed function for the dentate gyrus.
    CAS PubMed PubMed Central Google Scholar
  92. Deng, W., Saxe, M. D., Gallina, I. S. & Gage, F. H. Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain. J. Neurosci. 29, 13532–13542 (2009). This study showed that adult-born DGCs contribute to learning and memory before their full maturation, at a stage when they have enhanced excitability.
    CAS PubMed PubMed Central Google Scholar
  93. Zhang, C. L., Zou, Y., He, W., Gage, F. H. & Evans, R. M. A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451, 1004–1007 (2008).
    CAS PubMed Google Scholar
  94. Jessberger, S. et al. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learn. Mem. 16, 147–154 (2009).
    PubMed PubMed Central Google Scholar
  95. Madsen, T. M., Kristjansen, P. E., Bolwig, T. G. & Wortwein, G. Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat. Neuroscience 119, 635–642 (2003).
    CAS PubMed Google Scholar
  96. Snyder, J. S., Hong, N. S., McDonald, R. J. & Wojtowicz, J. M. A role for adult neurogenesis in spatial long-term memory. Neuroscience 130, 843–852 (2005).
    CAS PubMed Google Scholar
  97. Imayoshi, I. et al. Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nature Neurosci. 11, 1153–1161 (2008).
    CAS PubMed Google Scholar
  98. Warner-Schmidt, J. L., Madsen, T. M. & Duman, R. S. Electroconvulsive seizure restores neurogenesis and hippocampus-dependent fear memory after disruption by irradiation. Eur. J. Neurosci. 27, 1485–1493 (2008).
    PubMed Google Scholar
  99. Winocur, G., Wojtowicz, J. M., Sekeres, M., Snyder, J. S. & Wang, S. Inhibition of neurogenesis interferes with hippocampus-dependent memory function. Hippocampus 16, 296–304 (2006).
    PubMed Google Scholar
  100. Ko, H. G. et al. Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory. Mol. Brain 2, 1 (2009).
    PubMed PubMed Central Google Scholar
  101. Ben Abdallah, N. M., Slomianka, L., Vyssotski, A. L. & Lipp, H. P. Early age-related changes in adult hippocampal neurogenesis in C57 mice. Neurobiol. Aging 31, 151–161.
  102. Seki, T. & Arai, Y. Age-related production of new granule cells in the adult dentate gyrus. Neuroreport 6, 2479–2482 (1995).
    CAS PubMed Google Scholar
  103. Raber, J. et al. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat. Res. 162, 39–47 (2004).
    CAS PubMed Google Scholar
  104. Rola, R. et al. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp. Neurol. 188, 316–330 (2004).
    CAS PubMed Google Scholar
  105. Garthe, A., Behr, J. & Kempermann, G. Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLoS One 4, e5464 (2009).
    PubMed PubMed Central Google Scholar
  106. Nakashiba, T., Young, J. Z., McHugh, T. J., Buhl, D. L. & Tonegawa, S. Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning. Science 319, 1260–1264 (2008).
    CAS PubMed Google Scholar
  107. Brun, V. H. et al. Impaired spatial representation in CA1 after lesion of direct input from entorhinal cortex. Neuron 57, 290–302 (2008).
    CAS PubMed Google Scholar
  108. Gilbert, P. E., Kesner, R. P. & Lee, I. Dissociating hippocampal subregions: double dissociation between dentate gyrus and CA1. Hippocampus 11, 626–636 (2001).
    CAS PubMed Google Scholar
  109. Saxe, M. D. et al. Paradoxical influence of hippocampal neurogenesis on working memory. Proc. Natl Acad. Sci. USA 104, 4642–4646 (2007).
    CAS PubMed PubMed Central Google Scholar
  110. Zhang, F., Aravanis, A. M., Adamantidis, A., de Lecea, L. & Deisseroth, K. Circuit-breakers: optical technologies for probing neural signals and systems. Nature Rev. Neurosci. 8, 577–581 (2007).
    CAS Google Scholar
  111. Kitamura, T. et al. Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell 139, 814–827 (2009). The first study to show a role for adult hippocampal neurogenesis in system consolidation.
    CAS PubMed Google Scholar
  112. Kesner, R. P. A behavioral analysis of dentate gyrus function. Prog. Brain Res. 163, 567–576 (2007).
    PubMed Google Scholar
  113. Manganas, L. N. et al. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 318, 980–985 (2007).
    CAS PubMed PubMed Central Google Scholar
  114. Pereira, A. C. et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc. Natl Acad. Sci. USA 104, 5638–5643 (2007).
    CAS PubMed PubMed Central Google Scholar
  115. Amaral, D. G., Scharfman, H. E. & Lavenex, P. The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). Prog. Brain Res. 163, 3–22 (2007).
    PubMed PubMed Central Google Scholar
  116. Baker, J. L. Is there a support vector machine hiding in the dentate gyrus? Neurocomputing 52–54, 199–207 (2003).
    Google Scholar
  117. Houser, C. R. Interneurons of the dentate gyrus: an overview of cell types, terminal fields and neurochemical identity. Prog. Brain Res. 163, 217–232 (2007).
    CAS PubMed Google Scholar
  118. Jung, M. W. & McNaughton, B. L. Spatial selectivity of unit activity in the hippocampal granular layer. Hippocampus 3, 165–182 (1993).
    CAS PubMed Google Scholar
  119. Myers, C. E. & Scharfman, H. E. A role for hilar cells in pattern separation in the dentate gyrus: a computational approach. Hippocampus 19, 321–337 (2009).
    PubMed PubMed Central Google Scholar
  120. Henze, D. A., Wittner, L. & Buzsaki, G. Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo. Nature Neurosci. 5, 790–795 (2002).
    CAS PubMed Google Scholar
  121. Rolls, E. T. & Kesner, R. P. A computational theory of hippocampal function, and empirical tests of the theory. Prog. Neurobiol. 79, 1–48 (2006).
    CAS PubMed Google Scholar
  122. Hopfield, J. J. Neural networks and physical systems with emergent collective computational abilities. Proc. Natl Acad. Sci. USA 79, 2554–2558 (1982).
    CAS PubMed PubMed Central Google Scholar
  123. Dupret, D. et al. Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus. Eur. J. Neurosci. 22, 778–783 (2005).
    PubMed Google Scholar
  124. Monje, M. L., Toda, H. & Palmer, T. D. Inflammatory blockade restores adult hippocampal neurogenesis. Science 302, 1760–1765 (2003).
    CAS PubMed Google Scholar
  125. Garcia, A. D., Doan, N. B., Imura, T., Bush, T. G. & Sofroniew, M. V. GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nature Neurosci. 7, 1233–1241 (2004).
    CAS PubMed Google Scholar
  126. Farioli-Vecchioli, S. et al. The timing of differentiation of adult hippocampal neurons is crucial for spatial memory. PLoS Biol. 6, e246 (2008).
    PubMed PubMed Central Google Scholar

Download references