Wiring New Neurons with Old Circuits


The brain derives much of its function from its ability to adapt to tasks on a wide range of time scales, from milliseconds to days, weeks, and months. This adaptability at multiple time scales is found across all brain areas, from cognitive areas all the way to the peripheral areas, in which sensory information is encoded so as to facilitate the subsequent extraction of relevant information. The adaptability of the brain is achieved through multiple morphological and physiological changes occurring at all levels: from molecules, to spines, and to dendrites and axons. It is clear today that brain plasticity also operates at the level of entire cells. In at least two areas of the adult brain, new neurons are constitutively generated throughout life and form an integral part of the networks. Because the capacity of the adult brain to rewire itself depends on external influences, ongoing neuronal production represents also a plastic mechanism by which brain performance can be optimized according to the prevailing environment. However, it remains unclear when and why brain performance has to be optimized.

This chapter focuses on the functional issues linked to neurogenesis in the olfactory system. After outlining the processes of adult neurogenesis in the olfactory system and discussing their regulation by various factors, I consider how existing circuits can continue to work in the face of constant arrivals and departures of cells and explore the possible functional role of adult-born neurons in the host microcircuit. Concentrating exclusively on mammalian systems, I demonstrate throughout this chapter that adult neurogenesis is a plastic mechanism by which brain performance can be optimized to cope with changing environment or internal state.


Green Fluorescent Protein Granule Cell Olfactory Bulb Projection Neuron Adult Neurogenesis 
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.



I apologize to those authors whose references, although relevant to this subject, have not been included in this review for reasons of space constraints. My laboratory is supported by the Fondation pour la Recherche Médicale (Équipe FRM), by the life insurance company “AG2R-La-Mondiale,” and by Ecole des Neurosciences de Paris (ENP).


  1. Ache BW and Young JM (2005) Olfaction: diverse species, conserved principles. Neuron 48:417–430.PubMedGoogle Scholar
  2. Adrian ED (1942) Olfactory reactions in the brain of the hedgehog. J Physiol 100:459–473.PubMedGoogle Scholar
  3. Alonso M, Viollet C, Gabellec MM et al. (2006) Olfactory discrimination learning increases the survival of adult-born neurons in the olfactory bulb. J Neurosci 26:10508–10513.PubMedGoogle Scholar
  4. Altman J and Das GD (1965) Post-natal origin of microneurones in the rat brain. Nature 207:953–956.Google Scholar
  5. Alvarez-Buylla A (1990) Mechanism of neurogenesis in adult avian brain. Experientia 46:948–955.Google Scholar
  6. Alvarez-Buylla A and Garcia-Verdugo JM (2002) Neurogenesis in adult subventricular zone. J Neurosci 22:629–634.PubMedGoogle Scholar
  7. Alvarez-Buylla A, Garcia-Verdugo JM and Tramontin AD (2001) A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2:287–293.PubMedGoogle Scholar
  8. Ambrogini P, Orsini L, Mancini C et al. (2004) Learning may reduce neurogenesis in adult rat dentate gyrus. Neurosci Lett 359:13–16.PubMedGoogle Scholar
  9. Aungst JL, Heyward PM, Puche AC et al. (2003) Centre-surround inhibition among olfactory bulb glomeruli. Nature 426:623–629.Google Scholar
  10. Baker H, Kawano T, Margolis FL et al. (1983) Transneuronal regulation of tyrosine hydroxylase expression in olfactory bulb of mouse and rat. J Neurosci 3:69–78.PubMedGoogle Scholar
  11. Belluzzi O, Benedusi M, Ackman J et al. (2003) Electrophysiological differentiation of new neurons in the olfactory bulb. J Neurosci 23:10411–10418.PubMedGoogle Scholar
  12. Beltz BS and Sandeman DC (2003) Regulation of life-long neurogenesis in the decapod brain. Arthropod Struct Dev 32:39–60.PubMedGoogle Scholar
  13. Buck L, Axel R (1991) A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65:175–187.PubMedGoogle Scholar
  14. Carlén M, Cassidy RM, Brismar H et al. (2002) Functional integration of adult-born neurons. Curr Biol 12:606–608.PubMedGoogle Scholar
  15. Carleton A, Petreanu LT, Lansford R et al. (2003) Becoming a new neuron in the adult olfactory bulb. Nat Neurosci 6:507–518.PubMedGoogle Scholar
  16. Cecchi GA, Petreanu LT, Alvarez-Buylla A et al. (2001) Unsupervised learning and adaptation in a model of adult neurogenesis. J Comput Neurosci 11:175–182.PubMedGoogle Scholar
  17. Chambers RA, Potenza MN, Hoffman RE et al. (2004) Simulated apoptosis/neurogenesis regulates learning and memory capabilities of adaptive neural networks. Neuropsychopharmacology 29:747–758.PubMedGoogle Scholar
  18. Changeux JP and Danchin A (1976) Selective stabilisation of developing synapses as a mechanism for the specification of neuronal networks. Nature 264:705–712.Google Scholar
  19. Cleland TA and Linster C (2005) Computation in the olfactory system. Chem Senses 30:801–813.PubMedGoogle Scholar
  20. Davenne M, Custody C, Charneau P and Lledo P-M (2005) In vivo imaging of migrating neurons in the mammalian forebrain. Chem Senses 30:115–116.Google Scholar
  21. Davidson BL and Breakefield XO (2003) Viral vectors for gene delivery to the nervous system. Nat Rev Neurosci 4:353–364.PubMedGoogle Scholar
  22. Döbrössy MDE, Aurousseau C, Le Moal M et al. (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.PubMedGoogle Scholar
  23. Doetsch F (2003) A niche for adult neural stem cells. Curr Opin Genet Dev 13:543–550.PubMedGoogle Scholar
  24. Doetsch F, Caille I, Lim DA et al. (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716.PubMedGoogle Scholar
  25. Dupret D, Fabre A, Döbrössy MD et al. (2007) Spatial learning depends on both the addition and removal of new hippocampal neurons. PLoS Biol 5:e214.PubMedGoogle Scholar
  26. Ehninger D and 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
  27. Eisthen HL (1997) Evolution of vertebrate olfactory systems. Brain Behav Evol 50:222–233.PubMedGoogle Scholar
  28. Enwere E, Shingo T, Gregg C et al. (2004) Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci 24:8354–8365.PubMedGoogle Scholar
  29. Eriksson PS, Perfilieva E, Bjork-Eriksson T et al. (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317.PubMedGoogle Scholar
  30. Falk N, Holmstrom M, Carlen R et al. (2002) Gene delivery to adult neural stem cells. Exp Cell Res 279:34–39.PubMedGoogle Scholar
  31. Freeman WJ and Schneider W (1982) Changes in spatial patterns of rabbit olfactory EEG with conditioning to odors. Psychophysiology 19:44–56.PubMedGoogle Scholar
  32. Frielingsdorf H, Schwarz K, Brundin P et al. (2004) No evidence for new dopaminergic neurons in the adult mammalian substantia nigra. Proc Natl Acad Sci USA 101:10177–10182.PubMedGoogle Scholar
  33. Garcia AD, Doan NB, Imura T et al. (2004) GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci 7:1233–1241.PubMedGoogle Scholar
  34. Garcia-Verdugo JM, Doetsch F. Wichterle H et al. (1998) Architecture and cell types of the adult subventricular zone: in search of the stem cells. J Neurobiol 36:234–248.PubMedGoogle Scholar
  35. Gheusi G, Cremer H, McLean H et al. (2000) Importance of newly generated neurons in the adult OB for odor discrimination. Proc Natl Acad Sci USA 97:1823–1828.PubMedGoogle Scholar
  36. Goldman SA and Nottebohm F (1983) Neuronal production, migration and differentiation in a vocal control nucleus of the adult female canary brain. Proc Natl Acad Sci USA 80:2390–2394.PubMedGoogle Scholar
  37. Gould E, Reeves AJ, Graziano MS et al. (1999) Neurogenesis in the neocortex of the adult ­primates. Science 286:548–552.PubMedGoogle Scholar
  38. Grubb MS, Nissant A, Murray K and Lledo PM (2008) Functional maturation of the first synapse in olfaction: development and adult neurogenesis. J Neurosci 28:2919–2932.PubMedGoogle Scholar
  39. Hack MA, Saghatelyan A, de Chevigny et al. (2005) Neuronal fate determinants of adult olfactory bulb neurogenesis. Nat Neurosci 8:865–872.PubMedGoogle Scholar
  40. Hensch TK (2005) Critical period plasticity in local cortical circuits. Nat Rev Neurosci 6:877–888.PubMedGoogle Scholar
  41. Hildebrand JG and Shepherd GM (1997) Mechanisms of olfactory discrimination: converging evidence for common principles across phyla. Annu Rev Neurosci 20:595–631.PubMedGoogle Scholar
  42. Hinds JW (1968) Autoradiographic study of histogenesis in the mouse olfactory bulb. II. Cell proliferation and migration. J Comp Neurol 134: 305–322.PubMedGoogle Scholar
  43. Jakobsson J, Ericson C, Jansson M et al. (2003) Targeted transgene expression in rat brain using lentiviral vectors. J Neurosci Res 73:876–885.PubMedGoogle Scholar
  44. Kempermann G (2006) Adult neurogenesis. Oxford University Press, New York.Google Scholar
  45. Kohwi M, Osumi N, Rubenstein JL et al. (2005) Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb. J Neurosci 25:6997–7003.PubMedGoogle Scholar
  46. Kohwi M, Petryniak MA, Long JE et al. (2007) A subpopulation of olfactory bulb GABAergic interneurons is derived from Emx1- and Dlx5/6-expressing progenitors. J Neurosci 27:6878–6891.PubMedGoogle Scholar
  47. Koketsu D, Mikami A, Miyamoto Y et al. (2003) Nonrenewal of neurons in the cerebral neocortex of adult macaque monkeys. J Neurosci 23:937–942.PubMedGoogle Scholar
  48. Kornack DR and Rakic P (1999) Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci USA 96:5768–5773.PubMedGoogle Scholar
  49. Kornack DR and Rakic P (2001) Cell proliferation without neurogenesis in adult primate neocortex. Science 294:2127–2130.PubMedGoogle Scholar
  50. Kosaka T and Kosaka K (2005) Structural organization of the glomerulus in the main olfactory bulb. Chem Senses Suppl 1: i107–i108.Google Scholar
  51. Kosaka K et al. (1997) Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb. II. Prominent differences in the intraglomerular dendritic arborization and their relationship to olfactory nerve terminals. Neuroscience 76:775–786.PubMedGoogle Scholar
  52. Kosaka K et al. (1998) How simple is the organization of the olfactory glomerulus?: the heterogeneity of so-called periglomerular cells. Neurosci Res 30:101–110.PubMedGoogle Scholar
  53. Laywell ED, Rakic P, Kukekov VG et al. (2000) Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc Natl Acad Sci USA 97:13883–13888.PubMedGoogle Scholar
  54. Lemasson M, Saghatelyan A, Olivo-Marin JC et al. (2005) Neonatal and adult neurogenesis provide two distinct populations of granule cells in the mouse OB. J Neurosci 25:6816–6825.PubMedGoogle Scholar
  55. Lledo P-M and Gheusi G (2003) Olfactory processing in a changing brain. Neuroreport 14:1655–1663.PubMedGoogle Scholar
  56. Lledo P-M and Lagier S (2006) Local interneurons transduce spatial coding into temporal patterning in the mammalian olfactory bulb. Semin Cell Dev Biol 17:443–453.PubMedGoogle Scholar
  57. Lledo P-M and Saghatelyan A (2005) Integrating new neurons into the adult olfactory bulb: joining the network, life/death decisions, and the effects of sensory experience. Trends Neurosci 28:248–254.PubMedGoogle Scholar
  58. Lledo P-M, Gheusi G and Vincent JD (2005) Information processing in the mammalian olfactory system. Physiol Rev 85:281–317.PubMedGoogle Scholar
  59. Lois C and Alvarez-Buylla A (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264:1145–1148.PubMedGoogle Scholar
  60. Lois C, Hong EJ, Pease S et al. (2002) Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295:868–872.PubMedGoogle Scholar
  61. Magavi SSP, Mitchell BD, Szentirmai O et al. (2005) Adult-born and preexisting olfactory granule neurons undergo distinct experience-dependent modifications of their olfactory responses in vivo. J Neurosci 25:10729–10739.PubMedGoogle Scholar
  62. Malatesta P, Hack MA, Hartfuss E et al. (2003) Neuronal or glial progeny: regional differences in radial glia fate. Neuron 37:751–764.PubMedGoogle Scholar
  63. Malnic B, Hirono J, Sato T et al. (1999) Combinatorial receptor codes for odors. Cell 96:713–723.PubMedGoogle Scholar
  64. Mandairon N, Jourdan F and Didier A (2003) Deprivation of sensory inputs to the olfactory bulb up-regulates cell death and proliferation in the subventricular zone of adult mice. Neuroscience 119:507–516.PubMedGoogle Scholar
  65. Marshall CAG, Novitch BG and Goldman JE (2005) Olig2 directs astrocyte and oligodendrocyte formation in postnatal subventricular zone cells. J Neurosci 25:7289–7298.PubMedGoogle Scholar
  66. Mechawar N, Saghatelyan A, Grailhe R et al. (2004) Nicotinic receptors regulate the survival of newborn neurons in the adult OB. Proc Natl Acad Sci USA 101:9822–9826.PubMedGoogle Scholar
  67. Merkle FT, Mirzadeh Z and Alvarez-Buylla A (2007) Mosaic organization of neural stem cells in the adult brain. Science 317:381–384.PubMedGoogle Scholar
  68. Miwa N and Storm DR (2005) Odorant-induced activation of extracellular signal-regulated kinase/mitogen-activated protein kinase in the olfactory bulb promotes survival of newly formed granule cells. J Neurosci 25:5404–5412.PubMedGoogle Scholar
  69. Mizrahi A and Katz LC (2003) Dendritic stability in the adult olfactory bulb. Nat Neurosci 6:1201–1207.PubMedGoogle Scholar
  70. Mori K, Takahashi YK, Igarashi KM et al. (2006) Maps of odorant molecular features in the mammalian olfactory bulb. Physiol Rev 86:409–433.PubMedGoogle Scholar
  71. Morshead CM, Reynolds BA, Craig CG et al. (1994) Neural stem cells in the adults mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13:1071–1082.PubMedGoogle Scholar
  72. Nissant A, Bardy C, Katagiri H et al. (2009) Adult neurogenesis promotes synaptic plasticity in the olfactory bulb. Nat Neurosci 12:728–730.PubMedGoogle Scholar
  73. Oppenheim RW (1991) Cell death during development of the nervous system. Annu Rev Neurosci 14:453–501.PubMedGoogle Scholar
  74. Parrish-Aungst S, Shipley MT, Erdelyi et al. (2007) Quantitative analysis of neuronal diversity in the mouse olfactory bulb. J Comp Neurol 501:825–836.PubMedGoogle Scholar
  75. Peretto P, Merighi A, Fasolo A et al. (1997) Glial tubes in the rostral migratory stream of the adult rat. Brain Res Bull 42:9–21.PubMedGoogle Scholar
  76. Peretto P, Merighi A, Fasolo A et al. (1999) The subependymal layer in rodents: a site of structural plasticity and cell migration in the adult mammalian brain. Brain Res Bull 49:221–243.PubMedGoogle Scholar
  77. Petreanu L and Alvarez-Buylla A (2002) Maturation and death of adult-born OB granule neurons: Role of olfaction. J Neurosci 22:6106–6113.PubMedGoogle Scholar
  78. Philpot BD, Lim JH and Brunjes PC (1997) Activity-dependent regulation of calcium-binding proteins in the developing rat olfactory bulb. J Comp Neurol 387:12–26.PubMedGoogle Scholar
  79. Pressler RT and Strowbridge BW (2006) Blanes cells mediate persistent feedforward inhibition onto granule cells in the olfactory bulb. Neuron 49:889–904.PubMedGoogle Scholar
  80. Rakic P (2002) Adult neurogenesis in mammals, an identity crisis. J Neurosci 22:614–618.PubMedGoogle Scholar
  81. Rochefort C, Gheusi G, Vincent JD et al. (2002) Enriched odor exposure increases the number of newborn neurons in the adult OB and improves odor memory. J Neurosci 22:2679–2689.PubMedGoogle Scholar
  82. Rogelius N, Ericson C and Lundberg C (2005) In vivo labeling of neuroblasts in the subventricular zone of rats. J Neurosci Methods 142:285–293.PubMedGoogle Scholar
  83. Rubinson DA, Dillon CP, Kwiatkowski AV et al. (2003) A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet 33:401–406.PubMedGoogle Scholar
  84. Saghatelyan A, Roux P, Migliore M et al. (2005) Activity-dependent adjustments of the inhibitory network in the adult OB following early postnatal deprivation. Neuron 46:103–116.PubMedGoogle Scholar
  85. Schmidt-Hieber C, Jonas P and Bischofberger J (2004) Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429:184–187.Google Scholar
  86. Schoppa NE and Urban NN (2003) Dendritic processing within olfactory bulb circuits. Trends Neurosci 26:501–506.PubMedGoogle Scholar
  87. Scotto-Lomassese S, Strambi C, Strambi A et al. (2003) Suppression of adult neurogenesis impairs olfactory learning and memory in an adult insect. J Neurosci 23:9289–9296.PubMedGoogle Scholar
  88. Seri B, Garcia-Verdugo JM, McEwen BS and Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160.PubMedGoogle Scholar
  89. Shepherd GM (2006) Smell images and the flavour system in the human brain. Nature 444:316–321.Google Scholar
  90. Shepherd GM, Chen WR and Greer CA (2004) Olfactory bulb. In: Shepherd GM (ed) The synaptic organization of the brain (5th ed.), edited by Oxford University Press, New York, pp. 165–216.Google Scholar
  91. Shepherd GM, Chen WR, Willhite D et al. (2007) The olfactory granule cell: from classical enigma to central role in olfactory processing. Brain Res Rev 55:373–382.PubMedGoogle Scholar
  92. Shingo T, Gregg C, Enwere E et al. (2003) Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science 299:117–120.PubMedGoogle Scholar
  93. Shipley MT and Ennis M (1996) Functional organization of olfactory system. J Neurobiol 30:123–176.PubMedGoogle Scholar
  94. Stewart RR, Hoge GJ, Zigova T et al. (2002) Neural progenitor cells of the neonatal rat anterior subventricular zone express functional GABA(A) receptors. J Neurobiol 50:305–322.PubMedGoogle Scholar
  95. Stone DM, Grillo M, Margolis FL et al. (1991) Differential effect of functional olfactory bulb deafferentation on tyrosine hydroxylase and glutamic acid decarboxylase messenger RNA levels in rodent juxtaglomerular neurons. J Comp Neurol 311:223–233.PubMedGoogle Scholar
  96. Tiscornia G, Singer O, Ikawa M et al. (2003) A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA. Proc Natl Acad Sci USA 100:1844–1848.PubMedGoogle Scholar
  97. 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.PubMedGoogle Scholar
  98. Wachowiak M and Shipley MT (2006) Coding and synaptic processing of sensory information in the glomerular layer of the olfactory bulb. Semin Cell Dev Biol 17:411–423.PubMedGoogle Scholar
  99. Washbourne P and McAllister AK (2002) Techniques for gene transfer into neurons. Curr Opin Neurobiol 12:566–573.PubMedGoogle Scholar
  100. Whitman MC and Greer CA (2007) Synaptic integration of adult-generated olfactory bulb granule cells: basal axodendritic centrifugal input precedes apical dendrodendritic local circuits. J Neurosci 27:9951–9961.PubMedGoogle Scholar
  101. Willhite DC, Nguyen KT, Masurkar AV et al. (2006) Viral tracing identifies distributed columnar organization in the olfactory bulb. Proc Natl Acad Sci USA 103:12592–12597.PubMedGoogle Scholar
  102. Wilson RI and Mainen ZF (2006) Early events in olfactory processing. Annu Rev Neurosci 29:163–201.PubMedGoogle Scholar
  103. Winner B, Cooper-Kuhn CM, Aigner R et al. (2002) Long-term survival and cell death of newly generated neurons in the adult rat OB. Eur J Neurosci 16:1681–1689.PubMedGoogle Scholar
  104. Yamaguchi M and Mori K (2005) Critical period for sensory experience-dependent survival of newly generated granule cells in the adult mouse OB. Proc Natl Acad Sci USA 102: 9697–9702.PubMedGoogle Scholar
  105. Young JM, Friedman C, Williams EM et al. (2002) Different evolutionary processes shaped the mouse and human olfactory receptor gene families. Hum Mol Genet 11:535–546.PubMedGoogle Scholar
  106. Young KM, Fogarty M, Kessaris N et al. (2007) Subventricular zone stem cells are heterogeneous with respect to their embryonic origins and neurogenic fates in the adult olfactory bulb. J Neurosci 27:8286–8296.PubMedGoogle Scholar
  107. Zou DJ, Feinstein P, Rivers AL et al. (2004) Postnatal refinement of peripheral olfactory projections. Science 304:1976–1979.PubMedGoogle Scholar

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© Springer 2011

Authors and Affiliations

  1. 1.Laboratory for Perception and Memory, Department of NeuroscienceInstitut PasteurParisFrance
  2. 2.CNRS, URA2182ParisFrance

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