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Regulation of Adult Neurogenesis by Environment and Learning

  • Gerd Kempermann
Chapter

Abstract

Adult hippocampal neurogenesis is tightly linked to hippocampal ­function. This chapter covers the regulation of adult neurogenesis in response to either a relatively broad cognitive stimulus, an environmental enrichment, or ­specific learning situations. In contrast to more general behavioral stimuli, exemplified by voluntary wheel running, which induce precursor cell proliferation, such cognitive challenges promote the survival of newborn cells, presumably recruiting them for a specific function. Supposedly this function is closely related to the neuronal network, to which the new neurons are added; that is, the mossy fiber connection between the dentate gyrus, as the only location in which adult neurogenesis occurs in the hippocampus, and CA3. The key idea is that activity-dependent regulation of adult neurogenesis allows lifelong optimization of the mossy fiber connection, presumably allowing the system to efficiently respond to novelty and complexity encountered by the individual.

Keywords

Vascular Endothelial Growth Factor Dentate Gyrus Environmental Enrichment Adult Neurogenesis Newborn Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Aimone JB, Wiles J, Gage FH (2006) Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9:723–727.PubMedCrossRefGoogle Scholar
  2. Alahmed S, Herbert J (2008) Strain differences in proliferation of progenitor cells in the dentate gyrus of the adult rat and the response to fluoxetine are dependent on corticosterone. Neuroscience 157:677–682.PubMedCrossRefGoogle Scholar
  3. Becker S (2005) A computational principle for hippocampal learning and neurogenesis. Hippocampus 15:722–738.PubMedCrossRefGoogle Scholar
  4. Becker S, Wojtowicz JM (2007) A model of hippocampal neurogenesis in memory and mood disorders. Trends Cogn Sci 11:70–76.PubMedCrossRefGoogle Scholar
  5. Brandt MD, Jessberger S, Steiner B, Kronenberg G, Reuter K, Bick-Sander A, von der Behrens W, Kempermann G (2003) Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice. Mol Cell Neurosci 24:603–613.PubMedCrossRefGoogle Scholar
  6. Brown ES, Rush AJ, McEwen BS (1999) Hippocampal remodeling and damage by corticosteroids: Implications for mood disorders. Neuropsychopharmacology 21:474–484.PubMedCrossRefGoogle Scholar
  7. Bruel-Jungerman E, Davis S, Rampon C, Laroche S (2006) Long-term potentiation enhances neurogenesis in the adult dentate gyrus. J Neurosci 26:5888–5893.PubMedCrossRefGoogle Scholar
  8. Butz M, Lehmann K, Dammasch IE, Teuchert-Noodt G (2006) A theoretical network model to analyse neurogenesis and synaptogenesis in the dentate gyrus. Neural Netw 19:1490–1505.PubMedCrossRefGoogle Scholar
  9. Butz M, Teuchert-Noodt G, Grafen K, van Ooyen A (2008) Inverse relationship between adult hippocampal cell proliferation and synaptic rewiring in the dentate gyrus. Hippocampus 18:879–898.PubMedCrossRefGoogle Scholar
  10. Cameron HA, Gould E (1994) Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience 61:203–209.PubMedCrossRefGoogle Scholar
  11. Cameron HA, McEwen BS, Gould E (1995) Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J Neurosci 15:4687–4692.PubMedGoogle Scholar
  12. Cao L, Jiao X, Zuzga DS, Liu Y, Fong DM, Young D, During MJ (2004) VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 36:827–835.PubMedCrossRefGoogle Scholar
  13. Dobrossy MD, Drapeau E, Aurousseau C, Le Moal M, Piazza PV, Abrous DN (2003) 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.PubMedCrossRefGoogle Scholar
  14. Duman RS (2004) Depression: A case of neuronal life and death? Biol Psychiatry 56:140–145.PubMedCrossRefGoogle Scholar
  15. Dupret D, Fabre A, Dobrossy MD, Panatier A, Rodriguez JJ, Lamarque S, Lemaire V, Oliet SH, Piazza PV, Abrous DN (2007) Spatial learning depends on both the addition and removal of new hippocampal neurons. PLoS Biol 5:e214.PubMedCrossRefGoogle Scholar
  16. Dupret D, Revest JM, Koehl M, Ichas F, De Giorgi F, Costet P, Abrous DN, Piazza PV (2008) Spatial relational memory requires hippocampal adult neurogenesis. PLoS ONE 3:e1959.PubMedCrossRefGoogle Scholar
  17. Ehninger D, Kempermann G (2006) Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity. Genes Brain Behav 5:29–39.PubMedGoogle Scholar
  18. Fabel K, Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, Kuo CJ, Palmer TD (2003) VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci 18:2803–2812.PubMedCrossRefGoogle Scholar
  19. Fagiolini M, Fritschy JM, Low K, Mohler H, Rudolph U, Hensch TK (2004) Specific GABAA circuits for visual cortical plasticity. Science 303:1681–1683.PubMedCrossRefGoogle Scholar
  20. Feng R, Rampon C, Tang YP, Shrom D, Jin J, Kyin M, Sopher B, Martin GM, Kim SH, Langdon RB, Sisodia SS, Tsien JZ (2001) Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron 32:911–926.PubMedCrossRefGoogle Scholar
  21. Friedman WJ (2007) Comment on “Potential role for adult neurogenesis in the encoding of time in new memories”. Hippocampus 17:503–504.PubMedCrossRefGoogle Scholar
  22. Ge S, Goh EL, Sailor KA, Kitabatake Y, Ming GL, Song H (2006) GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439:589–593.CrossRefGoogle Scholar
  23. Ge S, Yang CH, Hsu KS, Ming GL, Song H (2007) A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54:559–566.PubMedCrossRefGoogle Scholar
  24. Gould E, Tanapat P (1999) Stress and hippocampal neurogenesis. Biol Psychiatry 46:1472–1479.PubMedCrossRefGoogle Scholar
  25. Gould E, Cameron HA, McEwen BS (1994) Blockade of NMDA receptors increases cell death and birth in the developing rat dentate gyrus. J Comp Neurol 340:551–565.PubMedCrossRefGoogle Scholar
  26. Gould E, McEwen BS, Tanapat P, Galea LAM, Fuchs E (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17:2492–2498.PubMedGoogle Scholar
  27. Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2:260–265.PubMedCrossRefGoogle Scholar
  28. Greenough WT, Cohen NJ, Juraska JM (1999) New neurons in old brains: Learning to survive? Nat Neurosci 2:203–205.PubMedCrossRefGoogle Scholar
  29. Hebb DO (1947) The effects of early experience on problem-solving at maturity. Am Psychol 2:306–307.Google Scholar
  30. Heine VM, Maslam S, Zareno J, Joels M, Lucassen PJ (2004) Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible. Eur J Neurosci 19:131–144.PubMedCrossRefGoogle Scholar
  31. Heine VM, Zareno J, Maslam S, Joels M, Lucassen PJ (2005) Chronic stress in the adult dentate gyrus reduces cell proliferation near the vasculature and VEGF and FLK-1 protein expression. Eur J Neurosci 21:1304–1314.PubMedCrossRefGoogle Scholar
  32. Hensch TK, Fagiolini M, Mataga N, Stryker MP, Baekkeskov S, Kash SF (1998) Local GABA circuit control of experience-dependent plasticity in developing visual cortex. Science 282:1504–1508.PubMedCrossRefGoogle Scholar
  33. Holick KA, Lee DC, Hen R, Dulawa SC (2008) Behavioral effects of chronic fluoxetine in BALB/cj mice do not require adult hippocampal neurogenesis or the serotonin 1a receptor. Neuropsychopharmacology 33:406–417.PubMedCrossRefGoogle Scholar
  34. Jacobs BL, Praag H, Gage FH (2000) Adult brain neurogenesis and psychiatry: A novel theory of depression. Mol Psychiatry 5:262–269.PubMedCrossRefGoogle Scholar
  35. Jessberger S, Kempermann G (2003) Adult-born hippocampal neurons mature into activity-dependent responsiveness. Eur J Neurosci 18:2707–2712.PubMedCrossRefGoogle Scholar
  36. Kee N, Teixeira CM, Wang AH, Frankland PW (2007a) Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci 10:355–362.PubMedCrossRefGoogle Scholar
  37. Kee N, Teixeira CM, Wang AH, Frankland PW (2007b) Imaging activation of adult-generated granule cells in spatial memory. Nat Protoc 2:3033–3044.PubMedCrossRefGoogle Scholar
  38. Kempermann G (2002) Why new neurons? Possible functions for adult hippocampal neurogen­esis. J Neurosci 22:635–638.PubMedGoogle Scholar
  39. Kempermann G (2008) The neurogenic reserve hypothesis: What is adult hippocampal neurogenesis good for? Trends Neurosci 31:163–169.PubMedCrossRefGoogle Scholar
  40. Kempermann G, Gage FH (1999) Experience-dependent regulation of adult hippocampal neurogenesis: Effects of long-term stimulation and stimulus withdrawal. Hippocampus 9:321–332.PubMedCrossRefGoogle Scholar
  41. Kempermann G, Gage FH (2002a) Genetic determinants of adult hippocampal neurogenesis correlate with acquisition, but not probe trial performance in the water maze task. Eur J Neurosci 16:129–136.PubMedCrossRefGoogle Scholar
  42. Kempermann G, Gage FH (2002b) Genetic influence on phenotypic differentiation in adult hippocampal neurogenesis. Brain Res Dev Brain Res 134:1–12.PubMedCrossRefGoogle Scholar
  43. Kempermann G, Kronenberg G (2003) Depressed new neurons? Adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression. Biol Psychiatry 54:499–503.PubMedCrossRefGoogle Scholar
  44. Kempermann G, Kuhn HG, Gage FH (1997a) Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc Natl Acad Sci USA 94:10409–10414.PubMedCrossRefGoogle Scholar
  45. Kempermann G, Kuhn HG, Gage FH (1997b) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495.CrossRefGoogle Scholar
  46. Kempermann G, Brandon EP, Gage FH (1998a) Environmental stimulation of 129/SvJ mice causes increased cell proliferation and neurogenesis in the adult dentate gyrus. Curr Biol 8:939–942.PubMedCrossRefGoogle Scholar
  47. Kempermann G, Kuhn HG, Gage FH (1998b) Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci 18:3206–3212.PubMedGoogle Scholar
  48. Kempermann G, Gast D, Gage FH (2002) Neuroplasticity in old age: Sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann Neurol 52:135–143.PubMedCrossRefGoogle Scholar
  49. Kempermann G, Chesler EJ, Lu L, Williams RW, Gage FH (2006) Natural variation and genetic covariance in adult hippocampal neurogenesis. Proc Natl Acad Sci USA 103:780–785.PubMedCrossRefGoogle Scholar
  50. Koehl M, Meerlo P, Gonzales D, Rontal A, Turek FW, Abrous DN (2008) Exercise-induced promotion of hippocampal cell proliferation requires beta-endorphin. FASEB J 22:2253–2262.PubMedCrossRefGoogle Scholar
  51. Kronenberg G, Reuter K, Steiner B, Brandt MD, Jessberger S, Yamaguchi M, Kempermann G (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–463.PubMedCrossRefGoogle Scholar
  52. Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D, Kempermann G (2006) Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging 27:1505–1513.PubMedCrossRefGoogle Scholar
  53. Magavi SS, Mitchell BD, Szentirmai O, Carter BS, Macklis JD (2005) Adult-born and preexisting olfactory granule neurons undergo distinct experience-dependent modifications of their olfactory responses in vivo. J Neurosci 25:10729–10739.PubMedCrossRefGoogle Scholar
  54. Mak GK, Enwere EK, Gregg C, Pakarainen T, Poutanen M, Huhtaniemi I, Weiss S (2007) Male pheromone-stimulated neurogenesis in the adult female brain: Possible role in mating behavior. Nat Neurosci 10:1003–1011.PubMedCrossRefGoogle Scholar
  55. Marashi V, Barnekow A, Ossendorf E, Sachser N (2003) Effects of different forms of environmental enrichment on behavioral, endocrinological, and immunological parameters in male mice. Horm Behav 43:281–292.PubMedCrossRefGoogle Scholar
  56. Matas-Rico E, Garcia-Diaz B, Llebrez-Zayas P, Lopez-Barroso D, Santin L, Pedraza C, Smith-Fernandez A, Fernandez-Llebrez P, Tellez T, Redondo M, Chun J, De Fonseca FR, Estivill-Torrus G (2008) Deletion of lysophosphatidic acid receptor LPA1 reduces neurogenesis in the mouse dentate gyrus. Mol Cell Neurosci 39:342–355.PubMedCrossRefGoogle Scholar
  57. Mohammed AH, Henriksson BG, Soderstrom S, Ebendal T, Olsson T, Seckl JR (1993) Environmental influences on the central nervous system and their implications for the aging rat. Behav Brain Res 57:183–191.PubMedCrossRefGoogle Scholar
  58. Nacher J, McEwen BS (2006) The role of N-methyl-d-asparate receptors in neurogenesis. Hippocampus 16:267–270.PubMedCrossRefGoogle Scholar
  59. Nacher J, Alonso-Llosa G, Rosell DR, McEwen BS (2003) NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus. Neurobiol Aging 24:273–284.PubMedCrossRefGoogle Scholar
  60. Okuyama N, Takagi N, Kawai T, Miyake-Takagi K, Takeo S (2004) Phosphorylation of extracellular-regulating kinase in NMDA receptor antagonist-induced newly generated neurons in the adult rat dentate gyrus. J Neurochem 88:717–725.PubMedCrossRefGoogle Scholar
  61. Petersen A, Wortwein G, Gruber SH, Mathe AA (2008) Escitalopram reduces increased ­hippocampal cytogenesis in a genetic rat depression model. Neurosci Lett 436:305–308.PubMedCrossRefGoogle Scholar
  62. Petrus DS, Fabel K, Kronenberg G, Winter C, Steiner B, Kempermann G (2009) NMDA and benzodiazepine receptors have synergistic and antagonistic effects on precursor cells in adult hippocampal neurogenesis. Eur J Neurosci 29(2):244–252.PubMedCrossRefGoogle Scholar
  63. Rochefort C, Gheusi G, Vincent JD, Lledo PM (2002) Enriched odor exposure increases the number of newborn neurons in the adult olfactory bulb and improves odor memory. J Neurosci 22:2679–2689.PubMedGoogle Scholar
  64. Rosenzweig MR, Bennett EL (1996) Psychobiology of plasticity: Effects of training and experience on brain and behavior. Behav Brain Res 78:57–65.PubMedCrossRefGoogle Scholar
  65. Rossi C, Angelucci A, Costantin L, Braschi C, Mazzantini M, Babbini F, Fabbri ME, Tessarollo L, Maffei L, Berardi N, Caleo M (2006) Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci 24:1850–1856.PubMedCrossRefGoogle Scholar
  66. Sahay A, Hen R (2007) Adult hippocampal neurogenesis in depression. Nat Neurosci 10:1110–1115.PubMedCrossRefGoogle Scholar
  67. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:805–809.PubMedCrossRefGoogle Scholar
  68. Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, Monckton JE, Garcia AD, Sofroniew MV, Kandel ER, Santarelli L, Hen R, Drew MR (2006) Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci USA 103:17501–17506.PubMedCrossRefGoogle Scholar
  69. Saxe MD, Malleret G, Vronskaya S, Mendez I, Garcia AD, Sofroniew MV, Kandel ER, Hen R (2007) Paradoxical influence of hippocampal neurogenesis on working memory. Proc Natl Acad Sci USA 104:4642–4646.PubMedCrossRefGoogle Scholar
  70. Schmidt-Hieber C, Jonas P, Bischofberger J (2004) Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429:184–187.CrossRefGoogle Scholar
  71. Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410:372–376.CrossRefGoogle Scholar
  72. Shors TJ, Townsend DA, Zhao M, Kozorovitskiy Y, Gould E (2002) Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 12:578–584.PubMedCrossRefGoogle Scholar
  73. Snyder JS, Hong NS, McDonald RJ, Wojtowicz JM (2005) A role for adult neurogenesis in spatial long-term memory. Neuroscience 130:843–852.PubMedCrossRefGoogle Scholar
  74. Steiner B, Zurborg S, Horster H, Fabel K, Kempermann G (2008) Differential 24 h responsiveness of prox1-expressing precursor cells in adult hippocampal neurogenesis to physical activity, environmental enrichment, and kainic acid-induced seizures. Neuroscience 154:521–529.PubMedCrossRefGoogle Scholar
  75. Stranahan AM, Khalil D, Gould E (2006) Social isolation delays the positive effects of running on adult neurogenesis. Nat Neurosci 9:526–533.PubMedCrossRefGoogle Scholar
  76. Tashiro A, Sandler VM, Toni N, Zhao C, Gage FH (2006) NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus. Nature 442:929–933.CrossRefGoogle Scholar
  77. Tashiro A, Makino H, Gage FH (2007) Experience-specific functional modification of the dentate gyrus through adult neurogenesis: A critical period during an immature stage. J Neurosci 27:3252–3259.PubMedCrossRefGoogle Scholar
  78. Tozuka Y, Fukuda S, Namba T, Seki T, Hisatsune T (2005) GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells. Neuron 47:803–815.PubMedCrossRefGoogle Scholar
  79. Trejo JL, Carro E, Torres-Aleman I (2001) Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 21:1628–1634.PubMedGoogle Scholar
  80. Van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270.PubMedCrossRefGoogle Scholar
  81. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional ­neurogenesis in the adult hippocampus. Nature 415:1030–1034.CrossRefGoogle Scholar
  82. Walsh RN, Cummins RA (1975) Mechanisms mediating the production of environmentally induced brain changes. Psychol Bull 82:986–1000.PubMedCrossRefGoogle Scholar
  83. Wang S, Scott BW, Wojtowicz JM (2000) Heterogeneous properties of dentate granule neurons in the adult rat. J Neurobiol 42:248–257.PubMedCrossRefGoogle Scholar
  84. Wang LP, Kempermann G, Kettenmann H (2005) A subpopulation of precursor cells in the mouse dentate gyrus receives synaptic GABAergic input. Mol Cell Neurosci 29:181–189.PubMedCrossRefGoogle Scholar
  85. Winocur G, Wojtowicz JM, Sekeres M, Snyder JS, Wang S (2006) Inhibition of neurogenesis interferes with hippocampus-dependent memory function. Hippocampus 16:296–304.PubMedCrossRefGoogle Scholar
  86. Wiskott L, Rasch MJ, Kempermann G (2006) A functional hypothesis for adult hippocampal neurogenesis: Avoidance of catastrophic interference in the dentate gyrus. Hippocampus 16:329–343.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  1. 1.Genomics of Regeneration, CRTD – Center for Regenerative Therapies DresdenDFG Forschungszentrum und ExcellenzclusterDresdenGermany

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