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New neurons for 'survival of the fittest'

Abstract

Adult neurogenesis is often considered an archaic trait that has undergone a 'phylogenetic reduction' from amphibian ancestors to humans. However, adult neurogenesis in the hippocampal dentate gyrus might actually be a late-evolved trait. In non-mammals, adult hippocampal neurogenesis is not restricted to the equivalents of the dentate gyrus, which also show different connectivity and functionality compared to their mammalian counterpart. Moving actively in a changing world and dealing with novelty and complexity regulate adult neurogenesis. New neurons might thus provide the cognitive adaptability to conquer ecological niches rich with challenging stimuli.

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Figure 1: Phylogenetic map of adult neurogenesis.
Figure 2: Phylogenetic comparison of the hippocampus.
Figure 3: Simplified scheme of the basic circuitry of the hippocampus.
Figure 4: The doublecortin stage of adult hippocampal neurogenesis.

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References

  1. Kaslin, J., Ganz, J. & Brand, M. Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain. Phil. Trans. R. Soc. B 363, 101–122 (2008).

    Article  PubMed  Google Scholar 

  2. Lindsey, B. W. & Tropepe, V. A comparative framework for understanding the biological principles of adult neurogenesis. Prog. Neurobiol. 80, 281–307 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Grandel, H., Kaslin, J., Ganz, J., Wenzel, I. & Brand, M. Neural stem cells and neurogenesis in the adult zebrafish brain: origin, proliferation dynamics, migration and cell fate. Dev. Biol. 295, 263–277 (2006).

    Article  CAS  PubMed  Google Scholar 

  4. Kempermann, G. Adult Neurogenesis 2 – Stem Cells and Neuronal Development in the Adult Brain (Oxford Univ. Press, 2011).

    Google Scholar 

  5. Cayre, M., Malaterre, J., Scotto-Lomassese, S., Strambi, C. & Strambi, A. The common properties of neurogenesis in the adult brain: from invertebrates to vertebrates. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 132, 1–15 (2002).

    Article  PubMed  Google Scholar 

  6. Barker, J. M., Boonstra, R. & Wojtowicz, J. M. From pattern to purpose: how comparative studies contribute to understanding the function of adult neurogenesis. Eur. J. Neurosci. 34, 963–977 (2011).

    Article  PubMed  Google Scholar 

  7. Barker, J. M., Wojtowicz, J. M. & Boonstra, R. Where's my dinner? Adult neurogenesis in free-living food-storing rodents. Genes Brain Behav. 4, 89–98 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Amrein, I. & Lipp, H. P. Adult hippocampal neurogenesis of mammals: evolution and life history. Biol. Lett. 5, 141–144 (2009).

    Article  PubMed  Google Scholar 

  9. Amrein, I., Lipp, H. P., Boonstra, R. & Wojtowicz, J. M. in Adult Neurogenesis (eds Gage, F., Kempermann, G. & Son, H.) 645–659 (Cold Spring Harbor Laboratory Press, 2008).

    Google Scholar 

  10. Amrein, I., Isler, K. & Lipp, H. P. Comparing adult hippocampal neurogenesis in mammalian species and orders: influence of chronological age and life history stage. Eur. J. Neurosci. 34, 978–987 (2011).

    Article  PubMed  Google Scholar 

  11. Ferretti, P. Is there a relationship between adult neurogenesis and neuron generation following injury across evolution? Eur. J. Neurosci. 34, 951–962 (2011).

    Article  PubMed  Google Scholar 

  12. Barnea, A. & Pravosudov, V. Birds as a model to study adult neurogenesis: bridging evolutionary, comparative and neuroethological approaches. Eur. J. Neurosci. 34, 884–907 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bateson, P. & Gluckman, P. Plasticity, Robustness, Development, and Evolution (Cambridge Univ. Press, 2011).

    Book  Google Scholar 

  14. Kempermann, G., Chesler, E. J., Lu, L., Williams, R. W. & Gage, F. H. Natural variation and genetic covariance in adult hippocampal neurogenesis. Proc. Natl Acad. Sci. USA 103, 780–785 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Plumpe, T. et al. Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation. BMC Neurosci. 7, 77 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kempermann, G. The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for? Trends Neurosci. 31, 163–169 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Siegrist, S. E., Haque, N. S., Chen, C. H., Hay, B. A. & Hariharan, I. K. Inactivation of both foxo and reaper promotes long-term adult neurogenesis in Drosophila. Curr. Biol. 20, 643–648 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Schmidt, M. Continuous neurogenesis in the olfactory brain of adult shore crabs, Carcinus maenas. Brain Res. 762, 131–143 (1997).

    Article  CAS  PubMed  Google Scholar 

  19. Bonfanti, L. & Ponti, G. Adult mammalian neurogenesis and the New Zealand white rabbit. Vet. J. 175, 310–331 (2008).

    Article  PubMed  Google Scholar 

  20. Amrein, I., Dechmann, D. K., Winter, Y. & Lipp, H. P. Absent or low rate of adult neurogenesis in the hippocampus of bats (Chiroptera). PLoS ONE 2, e455 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Huang, L., DeVries, G. J. & Bittman, E. L. Photoperiod regulates neuronal bromodeoxyuridine labeling in the brain of a seasonally breeding mammal. J. Neurobiol. 36, 410–420 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Altman, J. & Das, G. D. Postnatal neurogenesis in the guinea-pig. Nature 214, 1098–1101 (1967).

    Article  CAS  PubMed  Google Scholar 

  23. Perez-Martin, M. et al. Neurogenesis in explants from the walls of the lateral ventricle of adult bovine brain: role of endogenous IGF-1 as a survival factor. Eur. J. Neurosci. 17, 205–211 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Harman, A., Meyer, P. & Ahmat, A. Neurogenesis in the hippocampus of an adult marsupial. Brain Behav. Evol. 62, 1–12 (2003).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Knoth, R. et al. Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS ONE 5, e8809 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Curtis, M. A. et al. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315, 1243–1249 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Sanai, N. et al. Corridors of migrating neurons in the human brain and their decline during infancy. Nature 478, 382–386 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bergmann, O. et al. The age of olfactory bulb neurons in humans. Neuron 74, 634–639 (2012).

    Article  CAS  PubMed  Google Scholar 

  30. Sanai, N. et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427, 740–744 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Rakic, P. Limits of neurogenesis in primates. Science 227, 1054–1056 (1985).

    Article  CAS  PubMed  Google Scholar 

  32. 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  Google Scholar 

  33. Wehner, R., Boyer, M., Loertscher, F., Sommer, S. & Menzi, U. Ant navigation: one-way routes rather than maps. Curr. Biol. 16, 75–79 (2006).

    Article  CAS  PubMed  Google Scholar 

  34. Treves, A., Tashiro, A., Witter, M. E. & Moser, E. I. What is the mammalian dentate gyrus good for? Neuroscience 154, 1155–1172 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Li, G., Kataoka, H., Coughlin, S. R. & Pleasure, S. J. Identification of a transient subpial neurogenic zone in the developing dentate gyrus and its regulation by Cxcl12 and reelin signaling. Development 136, 327–335 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Wu, K. & Leung, L. S. Monosynaptic activation of CA3 by the medial perforant path. Brain Res. 797, 35–41 (1998).

    Article  CAS  PubMed  Google Scholar 

  37. Breindl, A., Derrick, B. E., Rodriguez, S. B. & Martinez, J. L. Jr. Opioid receptor-dependent long-term potentiation at the lateral perforant path–CA3 synapse in rat hippocampus. Brain Res. Bull. 33, 17–24 (1994).

    Article  CAS  PubMed  Google Scholar 

  38. Yeckel, M. F. & Berger, T. W. Feedforward excitation of the hippocampus by afferents from the entorhinal cortex: redefinition of the role of the trisynaptic pathway. Proc. Natl Acad. Sci. USA 87, 5832–5836 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  40. Kempermann, G. Why new neurons? Possible functions for adult hippocampal neurogenesis. J. Neurosci. 22, 635–638 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  42. Garthe, A., Behr, J. & Kempermann, G. Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLoS ONE 4, e5464 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Johnson, K. M., Boonstra, R. & Wojtowicz, J. M. Hippocampal neurogenesis in food-storing red squirrels: the impact of age and spatial behavior. Genes Brain Behav. 9, 583–591 (2010).

    CAS  PubMed  Google Scholar 

  44. Aimone, J. B., Deng, W. & Gage, F. H. Adult neurogenesis: integrating theories and separating functions. Trends Cogn. Sci. 14, 325–337 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Imayoshi, I. et al. Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nature Neurosci. 11, 1153–1161 (2008).

    Article  CAS  PubMed  Google Scholar 

  46. Kempermann, G. in Adult Neurogenesis 2 – Stem Cells and Neuronal Development in the Adult Brain Ch. 8 (ed. Kempermann, G.) 275–326 (Oxford Univ. Press, 2011).

    Google Scholar 

  47. Appleby, P. A., Kempermann, G. & Wiskott, L. The role of additive neurogenesis and synaptic plasticity in a hippocampal memory model with grid-cell like input. PLoS Comput. Biol. 7, e1001063 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lipp, H. P. Non-mental aspects of encephalisation: the forebrain as a playground of mammalian evolution. Hum. Evol. 4, 45–53 (1989).

    Article  Google Scholar 

  49. Amrein, I., Slomianka, L., Poletaeva, I. I., Bologova, N. V. & Lipp, H. P. Marked species and age-dependent differences in cell proliferation and neurogenesis in the hippocampus of wild-living rodents. Hippocampus 14, 1000–1010 (2004).

    Article  PubMed  Google Scholar 

  50. Colcombe, S. J. et al. Cardiovascular fitness, cortical plasticity, and aging. Proc. Natl Acad. Sci. USA 101, 3316–3321 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hermann, A. et al. Mesodermal cell types induce neurogenesis from adult human hippocampal progenitor cells. J. Neurochem. 98, 629–640 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Cayre, M. et al. Neurogenesis in adult insect mushroom bodies. J. Comp. Neurol. 371, 300–310 (1996).

    Article  CAS  PubMed  Google Scholar 

  53. Farris, S. M. & Roberts, N. S. Coevolution of generalist feeding ecologies and gyrencephalic mushroom bodies in insects. Proc. Natl Acad. Sci. USA 102, 17394–17399 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Herron, M. D. & Doebeli, M. Adaptive diversification of a plastic trait in a predictably fluctuating environment. J. Theor. Biol. 285, 58–68 (2011).

    Article  PubMed  Google Scholar 

  55. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Oelschlager, H. H., Haas-Rioth, M., Fung, C., Ridgway, S. H. & Knauth, M. Morphology and evolutionary biology of the dolphin (Delphinus sp.) brain-MR imaging and conventional histology. Brain Behav. Evol. 71, 68–86 (2008).

    Article  CAS  PubMed  Google Scholar 

  57. 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  PubMed  Google Scholar 

  58. Wang, S., Scott, B. W. & Wojtowicz, J. M. Heterogenous properties of dentate granule neurons in the adult rat. J. Neurobiol. 42, 248–257 (2000).

    Article  CAS  PubMed  Google Scholar 

  59. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Marin-Burgin, A., Mongiat, L. A., Pardi, M. B. & Schinder, A. F. Unique processing during a period of high excitation/inhibition balance in adult-born neurons. Science 335, 1238–1242 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Amrein, I. & Slomianka, L. A morphologically distinct granule cell type in the dentate gyrus of the red fox correlates with adult hippocampal neurogenesis. Brain Res. 1328, 12–24 (2010).

    Article  CAS  PubMed  Google Scholar 

  62. Jacobs, B. L., Praag, H. & Gage, F. H. Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol. Psychiatry 5, 262–269 (2000).

    Article  CAS  PubMed  Google Scholar 

  63. Reif, A., Schmitt, A., Fritzen, S. & Lesch, K. P. Neurogenesis and schizophrenia: dividing neurons in a divided mind? Eur. Arch. Psychiatry Clin. Neurosci. 257, 290–299 (2007).

    Article  PubMed  Google Scholar 

  64. Champagne-Lavau, M., Charest, A., Anselmo, K., Rodriguez, J. P. & Blouin, G. Theory of mind and context processing in schizophrenia: the role of cognitive flexibility. Psychiatry Res. 3 Jul 2012 (doi:10.1016/j.psychres.2012.06.011).

  65. Murphy, F. C., Michael, A. & Sahakian, B. J. Emotion modulates cognitive flexibility in patients with major depression. Psychol. Med. 42, 1373–1382 (2012).

    Article  CAS  PubMed  Google Scholar 

  66. Becker, S., Macqueen, G. & Wojtowicz, J. M. Computational modeling and empirical studies of hippocampal neurogenesis-dependent memory: effects of interference, stress and depression. Brain Res. 1299, 45–54 (2009).

    Article  CAS  PubMed  Google Scholar 

  67. Kappers, C. U. A., Huber, C. G. & Crosby, E. C. The Comparative Anatomy of the Nervous System of Vertebrates, including Man (Macmillan, 1936).

    Book  Google Scholar 

  68. Humphrey, T. in Evolution of the Forebrain (eds Hasler, R. & Stephan, H.) 104–116 (Plenum, 1967).

    Google Scholar 

  69. West, M. J. Stereological studies of the hippocampus: a comparison of the hippocampal subdivisions of diverse species including hedgehogs, laboratory rodents, wild mice and men. Prog. Brain Res. 83, 13–36 (1990).

    Article  CAS  PubMed  Google Scholar 

  70. Atoji, Y. & Wild, J. M. Anatomy of the avian hippocampal formation. Rev. Neurosci. 17, 3–15 (2006).

    Article  PubMed  Google Scholar 

  71. Kuhlenbeck, H. The Central Nervous System of Vertebrates. Derivatives of the Prosencephalon: Diencephalon and Telencephalon (Karger, 1977).

    Google Scholar 

  72. Barnea, A. & Nottebohm, F. Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees. Proc. Natl Acad. Sci. USA 91, 11217–11221 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Stephan, H. Evolutionary trends in limbic structures. Neurosci. Biobehav Rev. 7, 367–374 (1983).

    Article  CAS  PubMed  Google Scholar 

  74. Arlotta, P. & Macklis, J. D. Archeo-cell biology: carbon dating is not just for pots and dinosaurs. Cell 122, 4–6 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Spalding, K. L., Bhardwaj, R. D., Buchholz, B. A., Druid, H. & Frisen, J. Retrospective birth dating of cells in humans. Cell 122, 133–143 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. Spalding, K. L., Buchholz, B. A., Bergman, L. E., Druid, H. & Frisen, J. Forensics: age written in teeth by nuclear tests. Nature 437, 333–334 (2005).

    Article  CAS  PubMed  Google Scholar 

  77. Eisenstein, M. Positive fallout from the bomb. Nature Methods 2, 638–639 (2005).

    Article  CAS  PubMed  Google Scholar 

  78. Bhardwaj, R. D. et al. Neocortical neurogenesis in humans is restricted to development. Proc. Natl Acad. Sci. USA 103, 12564–12568 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Shankaran, M., King, C., Turner, H., Protasio, J. & Hellerstein, M. Sodium valproate increases neurogenesis in adult rat subventricular zone. Soc. Neurosci. Abstr. 572.4 (San Diego, California, USA, 13–17 Nov 2010).

  80. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Manganas, L. N. et al. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 318, 980–985 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ramm, P. et al. A nuclear magnetic resonance biomarker for neural progenitor cells: is it all neurogenesis? Stem Cells 27, 420–423 (2009).

    Article  CAS  PubMed  Google Scholar 

  83. Marichal, N., Garcia, G., Radmilovich, M., Trujillo-Cenoz, O. & Russo, R. E. Enigmatic central canal contacting cells: immature neurons in “standby mode”? J. Neurosci. 29, 10010–10024 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Gomez-Climent, M. A., Guirado, R., Varea, E. & Nacher, J. “Arrested development”. Immature, but not recently generated, neurons in the adult brain. Arch. Ital. Biol. 148, 159–172 (2010).

    CAS  PubMed  Google Scholar 

  85. Klempin, F., Kronenberg, G., Cheung, G., Kettenmann, H. & Kempermann, G. Properties of doublecortin-(DCX)-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice. PLoS ONE 6, e25760 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Cai, Y. et al. Doublecortin expression in adult cat and primate cerebral cortex relates to immature neurons that develop into GABAergic subgroups. Exp. Neurol. 216, 342–356 (2009).

    Article  CAS  PubMed  Google Scholar 

  87. Maddison, D. R. & Schulz, K. S. The Tree of Life Web Project [online], http://tolweb.org/tree/ (2007).

    Google Scholar 

  88. Marchioro, M. et al. Postnatal neurogenesis in the medial cortex of the tropical lizard Tropidurus hispidus. Neuroscience 134, 407–413 (2005).

    Article  CAS  PubMed  Google Scholar 

  89. Nacher, J. et al. CRMP-4 expression in the adult cerebral cortex and other telencephalic areas of the lizard Podarcis hispanica. Brain Res. Dev. Brain Res. 139, 285–294 (2002).

    Article  CAS  PubMed  Google Scholar 

  90. Wullimann, M. F. Secondary neurogenesis and telencephalic organization in zebrafish and mice: a brief review. Integr. Zool. 4, 123–133 (2009).

    Article  PubMed  Google Scholar 

  91. Brown, J. P. et al. Transient expression of doublecortin during adult neurogenesis. J. Comp. Neurol. 467, 1–10 (2003).

    Article  CAS  PubMed  Google Scholar 

  92. Moores, C. A. et al. Distinct roles of doublecortin modulating the microtubule cytoskeleton. EMBO J. 25, 4448–4457 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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The author thanks E. Brenowitz and P. Bateson for comments on the manuscript that have helped shape the evolutionary perspective.

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Kempermann, G. New neurons for 'survival of the fittest'. Nat Rev Neurosci 13, 727–736 (2012). https://doi.org/10.1038/nrn3319

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