Frontiers in Biology

, Volume 11, Issue 3, pp 193–213 | Cite as

Distribution and fate of DCX/PSA-NCAM expressing cells in the adult mammalian cortex: A local reservoir for adult cortical neuroplasticity?

  • Richard König
  • Bruno Benedetti
  • Peter Rotheneichner
  • Anna O’ Sullivan
  • Christina Kreutzer
  • Maria Belles
  • Juan Nacher
  • Thomas M. Weiger
  • Ludwig Aigner
  • Sébastien Couillard-Després


The expression of early developmental markers such as doublecortin (DCX) and the polysialylated-neural cell adhesion molecule (PSA-NCAM) has been used to identify immature neurons within canonical neurogenic niches. Additionally, DCX/PSA-NCAM+ immature neurons reside in cortical layer II of the paleocortex and in the paleo- and entorhinal cortex of mice and rats, respectively. These cells are also found in the neocortex of guinea pigs, rabbits, some afrotherian mammals, cats, dogs, non-human primates, and humans. The population of cortical DCX/PSA-NCAM+ immature neurons is generated prenatally as conclusively demonstrated in mice, rats, and guinea pigs. Thus, the majority of these cells do not appear to be the product of adult proliferative events. The immature neurons in cortical layer II are most abundant in the cortices of young individuals, while very few DCX/PSA-NCAM + cortical neurons can be detected in aged mammals. Maturation of DCX/PSA-NCAM+ cells into glutamatergic and GABAergic neurons has been proposed as an explanation for the age-dependent reduction in their population over time. In this review, we compile the recent information regarding the age-related decrease in the number of cortical DCX/PSA-NCAM+ neurons. We compare the distribution and fates of DCX/PSA-NCAM + neurons among mammalian species and speculate their impact on cognitive function. To respond to the diversity of adult neurogenesis research produced over the last number of decades, we close this review by discussing the use and precision of the term “adult non-canonical neurogenesis.”


aging cognition doublecortin piriform cortex plasticity neurogenesis 


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  1. Abrous D N, Montaron M F, Petry K G, Rougon G, Darnaudéry M, Le Moal M, Mayo W(1997). Decrease in highly polysialylated neuronal cell adhesion molecules and in spatial learning during ageing are not correlated. Brain Res, 744(2): 285–292PubMedCrossRefGoogle Scholar
  2. Ambrogini P, Cuppini R, Cuppini C, Ciaroni S, Cecchini T, Ferri P, Sartini S, Del Grande P (2000). Spatial learning affects immature granule cell survival in adult rat dentate gyrus. Neurosci Lett, 286(1): 21–24PubMedCrossRefGoogle Scholar
  3. Bédard A, Lévesque M, Bernier P J, Parent A (2002). The rostral migratory stream in adult squirrel monkeys: contribution of new neurons to the olfactory tubercle and involvement of the antiapoptotic protein Bcl-2. Eur J Neurosci, 16(10): 1917–1924PubMedCrossRefGoogle Scholar
  4. Bekkers J M, Suzuki N (2013). Neurons and circuits for odor processing in the piriform cortex. Trends Neurosci, 36(7): 429–438PubMedCrossRefGoogle Scholar
  5. Bernier P J, Bedard A, Vinet J, Levesque M, Parent A (2002). Newly generated neurons in the amygdala and adjoining cortex of adult primates. Proc Natl Acad Sci USA, 99(17): 11464–11469PubMedPubMedCentralCrossRefGoogle Scholar
  6. Betarbet R, Zigova T, Bakay R A, Luskin M B (1996). Dopaminergic and GABAergic interneurons of the olfactory bulb are derived from the neonatal subventricular zone. Int J Dev Neurosci, 14(7-8): 921–930PubMedCrossRefGoogle Scholar
  7. Biebl M, Cooper C M, Winkler J, Kuhn H G (2000). Analysis of neurogenesis and programmed cell death reveals a self-renewing capacity in the adult rat brain. Neurosci Lett, 291(1): 17–20PubMedCrossRefGoogle Scholar
  8. Bizon J L, Gallagher M (2005). More is less: neurogenesis and agerelated cognitive decline in Long-Evans rats. Sci SAGE KE, 2005(7): re2PubMedGoogle Scholar
  9. Bizon J L, Lee H J, Gallagher M (2004). Neurogenesis in a rat model of age-related cognitive decline. Aging Cell, 3(4): 227–234PubMedCrossRefGoogle Scholar
  10. Bloch J, Kaeser M, Sadeghi Y, Rouiller EM, Redmond D E, Brunet J F (2011). Doublecortin-positive cells in the adult primate cerebral cortex and possible role in brain plasticity and development. J Comp Neurol, 519(4): 775–789PubMedCrossRefGoogle Scholar
  11. Bondolfi L, Ermini F, Long J M, Ingram D K, Jucker M (2004). Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice. Neurobiol Aging, 25(3): 333–340PubMedCrossRefGoogle Scholar
  12. Bonfanti L (2013). The (real) neurogenic/gliogenic potential of the postnatal and adult brain parenchyma. ISRN Neurosci, 2013: 354136PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bonfanti L, Nacher J (2012). New scenarios for neuronal structural plasticity in non-neurogenic brain parenchyma: the case of cortical layer II immature neurons. Prog Neurobiol, 98(1): 1–15PubMedCrossRefGoogle Scholar
  14. Bonfanti L, Olive S, Poulain D A, Theodosis D T (1992). Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat: an immunohistochemical study. Neuroscience, 49(2): 419–436PubMedCrossRefGoogle Scholar
  15. Bonfanti L, Peretto P (2011). Adult neurogenesis in mammals—a theme with many variations. Eur J Neurosci, 34(6): 930–950PubMedCrossRefGoogle Scholar
  16. Breunig J J, Arellano J I, Macklis J D, Rakic P (2007). Everything that glitters isn’t gold: a critical review of postnatal neural precursor analyses. Cell Stem Cell, 1(6): 612–627PubMedCrossRefGoogle Scholar
  17. Brown J, Cooper-Kuhn C M, Kempermann G, van Praag H, Winkler J, Gage F H, Kuhn H G (2003). Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis. Eur J Neurosci, 17(10): 2042–2046PubMedCrossRefGoogle Scholar
  18. Burns K A, Ayoub A E, Breunig J J, Adhami F, Weng WL, Colbert MC, Rakic P, Kuan C Y (2007). Nestin-CreER mice reveal DNA synthesis by nonapoptotic neurons following cerebral ischemia hypoxia. Cereb Cortex, 17(11): 2585–2592PubMedCrossRefGoogle Scholar
  19. Burns T C, Ortiz-González X R, Gutiérrez-Pérez M, Keene C D, Sharda R, Demorest Z L, Jiang Y, Nelson-Holte M, Soriano M, Nakagawa Y, Luquin MR, Garcia-Verdugo JM, Prósper F, Low WC, Verfaillie C M (2006). Thymidine analogs are transferred from prelabeled donor to host cells in the central nervous system after transplantation: a word of caution. Stem Cells, 24(4): 1121–1127PubMedCrossRefGoogle Scholar
  20. Butt A M, Hamilton N, Hubbard P, Pugh M, Ibrahim M (2005). Synantocytes: the fifth element. J Anat, 207(6): 695–706PubMedPubMedCentralCrossRefGoogle Scholar
  21. Cai Y, Xiong K, Chu Y, Luo D W, Luo X G, Yuan X Y, Struble R G, Clough R W, Spencer D D, Williamson A, Kordower J H, Patrylo P R, Yan X X (2009). Doublecortin expression in adult cat and primate cerebral cortex relates to immature neurons that develop into GABAergic subgroups. Exp Neurol, 216(2): 342–356PubMedCrossRefGoogle Scholar
  22. Cameron H A, McKay R D (1999). Restoring production of hippocampal neurons in old age. Nat Neurosci, 2(10): 894–897PubMedCrossRefGoogle Scholar
  23. Carleton A, Petreanu L T, Lansford R, Alvarez-Buylla A, Lledo P M (2003). Becoming a new neuron in the adult olfactory bulb. Nat Neurosci, 6(5): 507–518PubMedGoogle Scholar
  24. Clarke L E, Young K M, Hamilton N B, Li H, Richardson W D, Attwell D (2012). Properties and fate of oligodendrocyte progenitor cells in the corpus callosum, motor cortex, and piriform cortex of the mouse. J Neurosci, 32(24): 8173–8185PubMedPubMedCentralCrossRefGoogle Scholar
  25. Costa M R, Kessaris N, Richardson W D, Götz M, Hedin-Pereira C (2007). The marginal zone/layer I as a novel niche for neurogenesis and gliogenesis in developing cerebral cortex. J Neurosci, 27(42): 11376–11388PubMedCrossRefGoogle Scholar
  26. Couillard-Despres S, Winner B, Karl C, Lindemann G, Schmid P, Aigner R, Laemke J, Bogdahn U, Winkler J, Bischofberger J, Aigner L (2006). Targeted transgene expression in neuronal precursors: watching young neurons in the old brain. Eur J Neurosci, 24(6): 1535–1545PubMedCrossRefGoogle Scholar
  27. Couillard-Despres S, Winner B, Schaubeck S, Aigner R, Vroemen M, Weidner N, Bogdahn U, Winkler J, Kuhn H G, Aigner L (2005). Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci, 21(1): 1–14PubMedCrossRefGoogle Scholar
  28. Curtis M A, Eriksson P S, Faull R L (2007). Progenitor cells and adult neurogenesis in neurodegenerative diseases and injuries of the basal ganglia. Clin Exp Pharmacol Physiol, 34(5-6): 528–532PubMedCrossRefGoogle Scholar
  29. Dawson M R, Polito A, Levine J M, Reynolds R (2003). NG2- expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Mol Cell Neurosci, 24(2): 476–488PubMedCrossRefGoogle Scholar
  30. Dayer A G, Cleaver K M, Abouantoun T, Cameron H A (2005). New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol, 168(3): 415–427PubMedPubMedCentralCrossRefGoogle Scholar
  31. de la Rosa-Prieto C, Saiz-Sanchez D, Ubeda-Bañon I, Argandoña-Palacios L, Garcia-Muñozguren S, Martinez-Marcos A (2010). Neurogenesis in subclasses of vomeronasal sensory neurons in adult mice. Dev Neurobiol, 70(14): 961–970PubMedCrossRefGoogle Scholar
  32. de Marchis S, Fasolo A, Puche A C (2004). Subventricular zone-derived neuronal progenitors migrate into the subcortical forebrain of postnatal mice. J Comp Neurol, 476(3): 290–300PubMedCrossRefGoogle Scholar
  33. de Nevi E, Marco-Salazar P, Fondevila D, Blasco E, Pérez L, Pumarola M (2013). Immunohistochemical study of doublecortin and nucleostemin in canine brain. Eur J Histochem, 57 (1): e9CrossRefGoogle Scholar
  34. des Portes V, Pinard J M, Billuart P, Vinet M C, Koulakoff A, Carrié A, Gelot A, Dupuis E, Motte J, Berwald-Netter Y, Catala M, Kahn A, Beldjord C, Chelly J (1998). A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. Cell, 92(1): 51–61PubMedCrossRefGoogle Scholar
  35. Dimou L, Simon C, Kirchhoff F, Takebayashi H, Götz M (2008). Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex. J Neurosci, 28(41): 10434–10442PubMedCrossRefGoogle Scholar
  36. Dirian L, Galant S, Coolen M, Chen W, Bedu S, Houart C, Bally-Cuif L, Foucher I (2014). Spatial regionalization and heterochrony in the formation of adult pallial neural stem cells. Dev Cell, 30(2): 123–136PubMedCrossRefGoogle Scholar
  37. Dityatev A, Dityateva G, Sytnyk V, Delling M, Toni N, Nikonenko I, Muller D, Schachner M (2004). Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses. J Neurosci, 24(42): 9372–9382PubMedCrossRefGoogle Scholar
  38. Doetsch F, García- Verdugo J M, Alvarez-Buylla A (1997). Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci, 17(13): 5046–5061PubMedGoogle Scholar
  39. Duque A, Rakic P (2011). Different effects of bromodeoxyuridine and [3H]thymidine incorporation into DNA on cell proliferation, position, and fate. J Neurosci, 31(42): 15205–15217PubMedPubMedCentralCrossRefGoogle Scholar
  40. Ehninger D, Kempermann G (2008). Neurogenesis in the adult hippocampus. Cell Tissue Res, 331(1): 243–250PubMedCrossRefGoogle Scholar
  41. Ehninger D, Wang L P, Klempin F, Römer B, Kettenmann H, Kempermann G (2011). Enriched environment and physical activity reduce microglia and influence the fate of NG2 cells in the amygdala of adult mice. Cell Tissue Res, 345(1): 69–86PubMedPubMedCentralCrossRefGoogle Scholar
  42. Ekstrand J J, Domroese M E, Feig S L, Illig K R, Haberly L B (2001). Immunocytochemical analysis of basket cells in rat piriform cortex. J Comp Neurol, 434(3): 308–328PubMedCrossRefGoogle Scholar
  43. Encinas J M, Michurina T V, Peunova N, Park J H, Tordo J, Peterson D A, Fishell G, Koulakov A, Enikolopov G (2011). Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell, 8(5): 566–579PubMedPubMedCentralCrossRefGoogle Scholar
  44. Englund C, Fink A, Lau C, Pham D, Daza R A, Bulfone A, Kowalczyk T, Hevner R F (2005). Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci, 25(1): 247–251PubMedCrossRefGoogle Scholar
  45. Eriksson P S, Perfilieva E, Björk-Eriksson T, Alborn A M, Nordborg C, Peterson D A, Gage F H (1998). Neurogenesis in the adult human hippocampus. Nat Med, 4(11): 1313–1317PubMedCrossRefGoogle Scholar
  46. Ernst A, Alkass K, Bernard S, Salehpour M, Perl S, Tisdale J, Possnert G, Druid H, Frisén J (2014). Neurogenesis in the striatum of the adult human brain. Cell, 156(5): 1072–1083PubMedCrossRefGoogle Scholar
  47. Feliciano D M, Bordey A (2013). Newborn cortical neurons: only for neonates? Trends Neurosci, 36(1): 51–61PubMedCrossRefGoogle Scholar
  48. Feliciano D M, Bordey A, Bonfanti L (2015). Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain. Cold Spring Harb Perspect Biol, 7(10): a018846PubMedCrossRefGoogle Scholar
  49. Fox G B, Fichera G, Barry T, O’Connell AW, Gallagher H C, Murphy K J, Regan C M (2000). Consolidation of passive avoidance learning is associated with transient increases of polysialylated neurons in layer II of the rat medial temporal cortex. J Neurobiol, 45(3): 135–141PubMedCrossRefGoogle Scholar
  50. Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet M C, Friocourt G, McDonnell N, Reiner O, Kahn A, McConnell S K, Berwald-Netter Y, Denoulet P, Chelly J (1999). Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron, 23(2): 247–256PubMedCrossRefGoogle Scholar
  51. Friocourt G, Liu J S, Antypa M, Rakic S, Walsh C A, Parnavelas J G (2007). Both doublecortin and doublecortin-like kinase play a role in cortical interneuron migration. J Neurosci, 27(14): 3875–3883PubMedCrossRefGoogle Scholar
  52. Gage F H, Kempermann G, Song H (2008). Adult Neurogenesis, Vol 52. Cold Spring Harbor Laboratory PressGoogle Scholar
  53. Ge S, Goh E L, Sailor K A, Kitabatake Y, Ming G L, Song H (2006). GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature, 439(7076): 589–593PubMedCrossRefGoogle Scholar
  54. Gómez-Climent M A, Castillo-Gómez E, Varea E, Guirado R, Blasco-Ibáñez J M, Crespo C, Martínez-Guijarro F J, Nácher J (2008). A population of prenatally generated cells in the rat paleocortex maintains an immature neuronal phenotype into adulthood. Cereb Cortex, 18(10): 2229–2240PubMedCrossRefGoogle Scholar
  55. Gomez-Climent M A, Guirado R, Varea E, Nàcher J (2010). “Arrested development”. Immature, but not recently generated, neurons in the adult brain. Arch Ital Biol, 148(2): 159–172Google Scholar
  56. Gottfried J A, Winston J S, Dolan R J (2006). Dissociable codes of odor quality and odorant structure in human piriform cortex. Neuron, 49 (3): 467–479PubMedCrossRefGoogle Scholar
  57. Gould E (2007).How widespread is adult neurogenesis in mammals? Nat Rev Neurosci, 8(6): 481–488Google Scholar
  58. Gould E, Tanapat P, Hastings N B, Shors T J (1999). Neurogenesis in adulthood: a possible role in learning. Trends Cogn Sci, 3(5): 186–192PubMedCrossRefGoogle Scholar
  59. Gritti A, Vescovi A L, Galli R (2002). Adult neural stem cells: plasticity and developmental potential. J Physiol Paris, 96(1-2): 81–90PubMedCrossRefGoogle Scholar
  60. Guo F, Maeda Y, Ma J, Xu J, Horiuchi M, Miers L, Vaccarino F, Pleasure D (2010). Pyramidal neurons are generated from oligodendroglial progenitor cells in adult piriform cortex. J Neurosci, 30(36): 12036–12049PubMedPubMedCentralCrossRefGoogle Scholar
  61. Hastings N B, Gould E (1999). Rapid extension of axons into the CA3 region by adult-generated granule cells. J Comp Neurol, 413(1): 146–154PubMedCrossRefGoogle Scholar
  62. He X, Zhang X M, Wu J, Fu J, Mou L, Lu D H, Cai Y, Luo X G, Pan A, Yan X X (2014). Olfactory experience modulates immature neuron development in postnatal and adult guinea pig piriform cortex. Neuroscience, 259: 101–112PubMedCrossRefGoogle Scholar
  63. Hevner R F, Hodge R D, Daza R A, Englund C (2006). Transcription factors in glutamatergic neurogenesis: conserved programs in neocortex, cerebellum, and adult hippocampus. Neurosci Res, 55 (3): 223–233PubMedCrossRefGoogle Scholar
  64. Johnson C P, Fujimoto I, Rutishauser U, Leckband D E (2005). Direct evidence that neural cell adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion. J Biol Chem, 280(1): 137–145PubMedCrossRefGoogle Scholar
  65. Kadohisa M, Wilson D A (2006a). Olfactory cortical adaptation facilitates detection of odors against background. J Neurophysiol, 95(3): 1888–1896PubMedCrossRefGoogle Scholar
  66. Kadohisa M, Wilson D A (2006b). Separate encoding of identity and similarity of complex familiar odors in piriform cortex. Proc Natl Acad Sci USA, 103(41): 15206–15211PubMedPubMedCentralCrossRefGoogle Scholar
  67. Kang S H, Fukaya M, Yang J K, Rothstein J D, Bergles D E (2010). NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. Neuron, 68(4): 668–681PubMedPubMedCentralCrossRefGoogle Scholar
  68. Kaplan M S (1981). Neurogenesis in the 3-month-old rat visual cortex. J Comp Neurol, 195(2): 323–338PubMedCrossRefGoogle Scholar
  69. Kapur A, Pearce R A, Lytton W W, Haberly L B (1997). GABAAmediated IPSCs in piriform cortex have fast and slow components with different properties and locations on pyramidal cells. J Neurophysiol, 78(5): 2531–2545PubMedGoogle Scholar
  70. Kato T, Yokouchi K, Kawagishi K, Fukushima N, Miwa T, Moriizumi T, Kato T, Yokouchi K, Kawagishi K (2000). Fate of newly formed periglomerular cells in the olfactory bulb. Acta Otolaryngol, 120(7): 876–879PubMedCrossRefGoogle Scholar
  71. Kelsch W, Mosley C P, Lin C W, Lois C (2007). Distinct mammalian precursors are committed to generate neurons with defined dendritic projection patterns. PLoS Biol, 5 (11): e300CrossRefGoogle Scholar
  72. Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004). Milestones of neuronal development in the adult hippocampus. Trends Neurosci, 27(8): 447–452PubMedCrossRefGoogle Scholar
  73. Klempin F, Kronenberg G, Cheung G, Kettenmann H, Kempermann G (2011). Properties of doublecortin-(DCX)-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice. PLoS ONE, 6 (10): e25760CrossRefGoogle Scholar
  74. Komitova M, Zhu X, Serwanski D R, Nishiyama A (2009). NG2 cells are distinct from neurogenic cells in the postnatal mouse subventricular zone. J Comp Neurol, 512(5): 702–716PubMedPubMedCentralCrossRefGoogle Scholar
  75. König R, Rotheneichner P, Marschallinger J, Aigner L, Couillard-Despres S (2016). Adult Neurogenesis in the Hippocampus. Elsevier, pp. 145–176Google Scholar
  76. Kornack D R, Rakic P (2001). Cell proliferation without neurogenesis in adult primate neocortex. Science, 294(5549): 2127–2130PubMedCrossRefGoogle Scholar
  77. Kremer T, Jagasia R, Herrmann A, Matile H, Borroni E, Francis F, Kuhn H G, Czech C (2013). Analysis of adult neurogenesis: evidence for a prominent “non-neurogenic” DCX-protein pool in rodent brain. PLoS ONE, 8 (5): e59269CrossRefGoogle Scholar
  78. Kuan C Y, Schloemer A J, Lu A, Burns K A, WengW L, Williams M T, Strauss K I, Vorhees C V, Flavell R A, Davis R J, Sharp F R, Rakic P (2004). Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying neurons in adult rodent brain. J Neurosci, 24 (47): 10763–10772PubMedPubMedCentralCrossRefGoogle Scholar
  79. Kunz B A, Kohalmi S E (1991). Modulation of mutagenesis by deoxyribonucleotide levels. Annu Rev Genet, 25(1): 339–359PubMedCrossRefGoogle Scholar
  80. Lehner B, Sandner B, Marschallinger J, Lehner C, Furtner T, Couillard- Despres S, Rivera F J, Brockhoff G, Bauer H C, Weidner N, Aigner L (2011). The dark side of BrdU in neural stem cell biology: detrimental effects on cell cycle, differentiation and survival. Cell Tissue Res, 345(3): 313–328PubMedCrossRefGoogle Scholar
  81. Lemaire V, Koehl M, Le Moal M, Abrous D N (2000). Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci USA, 97(20): 11032–11037PubMedPubMedCentralCrossRefGoogle Scholar
  82. Luskin M B, Boone M S (1994). Rate and pattern of migration of lineally-related olfactory bulb interneurons generated postnatally in the subventricular zone of the rat. Chem Senses, 19(6): 695–714PubMedCrossRefGoogle Scholar
  83. Luzzati F, Bonfanti L, Fasolo A, Peretto P (2009). DCX and PSANCAM expression identifies a population of neurons preferentially distributed in associative areas of different pallial derivatives and vertebrate species. Cereb Cortex, 19(5): 1028–1041PubMedCrossRefGoogle Scholar
  84. Luzzati F, Nato G, Oboti L, Vigna E, Rolando C, Armentano M, Bonfanti L, Fasolo A, Peretto P (2014). Quiescent neuronal progenitors are activated in the juvenile guinea pig lateral striatum and give rise to transient neurons. Development, 141(21): 4065–4075PubMedCrossRefGoogle Scholar
  85. Luzzati F, Peretto P, Aimar P, Ponti G, Fasolo A, Bonfanti L (2003). Glia-independent chains of neuroblasts through the subcortical parenchyma of the adult rabbit brain. Proc Natl Acad Sci USA, 100(22): 13036–13041PubMedPubMedCentralCrossRefGoogle Scholar
  86. Manganas L N, Zhang X, Li Y, Hazel R D, Smith S D, Wagshul M E, Henn F, Benveniste H, Djuric P M, Enikolopov G, Maletic-Savatic M (2007). Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science, 318(5852): 980–985PubMedPubMedCentralCrossRefGoogle Scholar
  87. Markakis E A, Gage F H (1999). Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles. J Comp Neurol, 406(4): 449–460PubMedCrossRefGoogle Scholar
  88. Martí-Mengual U, Varea E, Crespo C, Blasco-Ibáñez J M, Nacher J (2013). Cells expressing markers of immature neurons in the amygdala of adult humans. Eur J Neurosci, 37(1): 10–22PubMedCrossRefGoogle Scholar
  89. Mikkonen M, Soininen H, Kälviänen R, Tapiola T, Ylinen A, Vapalahti M, Paljärvi L, Pitkänen A (1998). Remodeling of neuronal circuitries in human temporal lobe epilepsy: increased expression of highly polysialylated neural cell adhesion molecule in the hippocampus and the entorhinal cortex. Ann Neurol, 44(6): 923–934PubMedCrossRefGoogle Scholar
  90. Murphy K J, Fox G B, Foley A G, Gallagher H C, O’Connell A, Griffin A M, Nau H, Regan C M (2001). Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning, and attenuates age-related NCAM-mediated neuroplastic decline within the rat medial temporal lobe. J Neurochem, 78(4): 704–714PubMedCrossRefGoogle Scholar
  91. Nacher J, Bonfanti L (2015). New neurons from old beliefs in the adult piriform cortex? A Commentary on: “Occurrence of new neurons in the piriform cortex”. Front Neuroanat, 9: 62PubMedPubMedCentralCrossRefGoogle Scholar
  92. Nacher J, Crespo C, McEwen B S (2001). Doublecortin expression in the adult rat telencephalon. Eur J Neurosci, 14(4): 629–644PubMedCrossRefGoogle Scholar
  93. Nacher J, Lanuza E, McEwen B S (2002). Distribution of PSA-NCAM expression in the amygdala of the adult rat. Neuroscience, 113(3): 479–484PubMedCrossRefGoogle Scholar
  94. Neville K R, Haberly L B (2003). Beta and gamma oscillations in the olfactory system of the urethane-anesthetized rat. J Neurophysiol, 90 (6): 3921–3930PubMedCrossRefGoogle Scholar
  95. Ní Dhúill C M, Fox G B, Pittock S J, O’Connell A W, Murphy K J, Regan C M (1999). Polysialylated neural cell adhesion molecule expression in the dentate gyrus of the human hippocampal formation from infancy to old age. J Neurosci Res, 55(1): 99–106PubMedCrossRefGoogle Scholar
  96. Nishiyama A, Komitova M, Suzuki R, Zhu X (2009). Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci, 10(1): 9–22PubMedCrossRefGoogle Scholar
  97. Nishiyama A, Suzuki R, Zhu X (2014). NG2 cells (polydendrocytes) in brain physiology and repair. Front Neurosci, 8: 133PubMedPubMedCentralCrossRefGoogle Scholar
  98. Nowakowski R S, Hayes N L (2000). New neurons: extraordinary evidence or extraordinary conclusion? Science, 288 (5467): 771PubMedCrossRefGoogle Scholar
  99. Nowakowski R S, Lewin S B, Miller M W (1989). Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population. J Neurocytol, 18(3): 311–318PubMedCrossRefGoogle Scholar
  100. Okuda H, Tatsumi K, Makinodan M, Yamauchi T, Kishimoto T, Wanaka A (2009). Environmental enrichment stimulates progenitor cell proliferation in the amygdala. J Neurosci Res, 87(16): 3546–3553PubMedCrossRefGoogle Scholar
  101. Patzke N, Le Roy A, Ngubane N W, Bennett N C, Medger K, Gravett N, Kaswera-Kyamakya C, Gilissen E, Chawana R, Manger P R (2014). The distribution of doublecortin-immunopositive cells in the brains of four afrotherian mammals: the Hottentot golden mole (Amblysomus hottentotus), the rock hyrax (Procavia capensis), the eastern rock sengi (Elephantulus myurus) and the four-toed sengi (Petrodromus tetradactylus). Brain Behav Evol, 84(3): 227–241PubMedCrossRefGoogle Scholar
  102. Peretto P, Bonfanti L (2014). Major unsolved points in adult neurogenesis: doors open on a translational future? Front Neurosci, 8: 154PubMedPubMedCentralCrossRefGoogle Scholar
  103. Petreanu L, Alvarez-Buylla A (2002). Maturation and death of adultborn olfactory bulb granule neurons: role of olfaction. J Neurosci, 22 (14): 6106–6113PubMedGoogle Scholar
  104. Pierce A A, Xu A W (2010). De novo neurogenesis in adult hypothalamus as a compensatory mechanism to regulate energy balance. J Neurosci, 30(2): 723–730PubMedPubMedCentralCrossRefGoogle Scholar
  105. Psachoulia K, Jamen F, Young K M, Richardson W D (2009). Cell cycle dynamics of NG2 cells in the postnatal and ageing brain. Neuron Glia Biol, 5(3-4): 57–67PubMedCrossRefGoogle Scholar
  106. Purves D, Augustine G J, Flitzpatrick D, Katz L C, La Mantia A S, McNamara J O, Williams S M (2001). Neuroscience, 2nd edition. Sunderland (MA): Sinauer AssociatesGoogle Scholar
  107. Richardson W D, Young K M, Tripathi R B, McKenzie I (2011). NG2- glia as multipotent neural stem cells: fact or fantasy? Neuron, 70(4): 661–673PubMedPubMedCentralCrossRefGoogle Scholar
  108. Rivers L E, Young K M, Rizzi M, Jamen F, Psachoulia K, Wade A, Kessaris N, Richardson W D (2008). PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci, 11(12): 1392–1401PubMedCrossRefGoogle Scholar
  109. Robins S C, Trudel E, Rotondi O, Liu X, Djogo T, Kryzskaya D, Bourque CW, KokoevaMV (2013). Evidence for NG2-glia derived, adult-born functional neurons in the hypothalamus. PLoS ONE, 8 (10): e78236PubMedPubMedCentralCrossRefGoogle Scholar
  110. Rosselli-Austin L, Altman J (1979). The postnatal development of the main olfactory bulb of the rat. J Dev Physiol, 1(4): 295–313PubMedGoogle Scholar
  111. Rossi S L, Mahairaki V, Zhou L, Song Y, Koliatsos V E (2014). Remodeling of the piriform cortex after lesion in adult rodents. Neuroreport, 25(13): 1006–1012PubMedPubMedCentralCrossRefGoogle Scholar
  112. Rubio A, Belles M, Belenguer G, Vidueira S, Fariñas I, Nacher J (2015). Characterization and isolation of immature neurons of the adult mouse piriform cortex. Dev Neurobiol, doi: 10.1002/dneu.22357Google Scholar
  113. Rutishauser U (2008). Polysialic acid in the plasticity of the developing and adult vertebrate nervous system. Nat Rev Neurosci, 9(1): 26–35PubMedCrossRefGoogle Scholar
  114. Saegusa T, Mine S, Iwasa H, Murai H, Seki T, Yamaura A, Yuasa S (2004). Involvement of highly polysialylated neural cell adhesion molecule (PSA-NCAM)-positive granule cells in the amygdaloidkindling- induced sprouting of a hippocampal mossy fiber trajectory. Neurosci Res, 48(2): 185–194PubMedCrossRefGoogle Scholar
  115. Sairanen M, O’Leary O F, Knuuttila J E, Castrén E (2007). Chronic antidepressant treatment selectively increases expression of plasticity- related proteins in the hippocampus and medial prefrontal cortex of the rat. Neuroscience, 144(1): 368–374PubMedCrossRefGoogle Scholar
  116. Sanai N, Nguyen T, Ihrie R A, Mirzadeh Z, Tsai H H, Wong M, Gupta N, Berger M S, Huang E, Garcia-Verdugo J M, Rowitch D H, Alvarez- Buylla A (2011). Corridors of migrating neurons in the human brain and their decline during infancy. Nature, 478(7369): 382–386PubMedPubMedCentralCrossRefGoogle Scholar
  117. Seki T, Arai Y (1999). Temporal and spacial relationships between PSANCAM- expressing, newly generated granule cells, and radial glialike cells in the adult dentate gyrus. J Comp Neurol, 410(3): 503–513PubMedCrossRefGoogle Scholar
  118. Shapiro L A, Ng K, Zhou Q Y, Ribak C E (2009). Subventricular zonederived, newly generated neurons populate several olfactory and limbic forebrain regions. Epilepsy Behav, 14(Suppl 1): 74–80PubMedCrossRefGoogle Scholar
  119. Shapiro L A, Ng K L, Kinyamu R, Whitaker-Azmitia P, Geisert E E, Blurton-Jones M, Zhou Q Y, Ribak C E (2007a). Origin, migration and fate of newly generated neurons in the adult rodent piriform cortex. Brain Struct Funct, 212(2): 133–148PubMedCrossRefGoogle Scholar
  120. Shapiro L A, Ng K L, Zhou Q Y, Ribak C E (2007b). Olfactory enrichment enhances the survival of newly born cortical neurons in adult mice. Neuroreport, 18(10): 981–985PubMedCrossRefGoogle Scholar
  121. Shechter R, Ziv Y, Schwartz M (2007). New GABAergic interneurons supported by myelin-specific T cells are formed in intact adult spinal cord. Stem Cells, 25(9): 2277–2282PubMedCrossRefGoogle Scholar
  122. Shors T J, 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(6826): 372–376PubMedCrossRefGoogle Scholar
  123. Shors T J, Townsend D A, Zhao M, Kozorovitskiy Y, Gould E (2002). Neurogenesis may relate to some but not all types of hippocampaldependent learning. Hippocampus, 12(5): 578–584PubMedPubMedCentralCrossRefGoogle Scholar
  124. Spalding K L, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner H B, Boström E, Westerlund I, Vial C, Buchholz B A, Possnert G, Mash D C, Druid H, Frisén J (2013). Dynamics of hippocampal neurogenesis in adult humans. Cell, 153(6): 1219–1227PubMedPubMedCentralCrossRefGoogle Scholar
  125. Suzuki N, Bekkers J M (2007). Inhibitory interneurons in the piriform cortex. Clin Exp Pharmacol Physiol, 34(10): 1064–1069PubMedCrossRefGoogle Scholar
  126. Suzuki N, Bekkers J M (2010a). Distinctive classes of GABAergic interneurons provide layer-specific phasic inhibition in the anterior piriform cortex. Cereb Cortex, 20(12): 2971–2984PubMedPubMedCentralCrossRefGoogle Scholar
  127. Suzuki N, Bekkers J M (2010b). Inhibitory neurons in the anterior piriform cortex of the mouse: classification using molecular markers. J Comp Neurol, 518(10): 1670–1687PubMedCrossRefGoogle Scholar
  128. Takemura N U (2005). Evidence for neurogenesis within the white matter beneath the temporal neocortex of the adult rat brain. Neuroscience, 134(1): 121–132PubMedCrossRefGoogle Scholar
  129. Toni N, Laplagne D A, Zhao C, Lombardi G, Ribak C E, Gage F H, Schinder A F (2008). Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci, 11(8): 901–907PubMedPubMedCentralCrossRefGoogle Scholar
  130. Toni N, Teng EM, Bushong E A, Aimone J B, Zhao C, Consiglio A, van Praag H, Martone M E, Ellisman M H, Gage F H (2007). Synapse formation on neurons born in the adult hippocampus. Nat Neurosci, 10(6): 727–734PubMedCrossRefGoogle Scholar
  131. van Praag H, Schinder A F, Christie B R, Toni N, Palmer T D, Gage F H (2002). Functional neurogenesis in the adult hippocampus. Nature, 415(6875): 1030–1034PubMedCrossRefGoogle Scholar
  132. Varea E, Belles M, Vidueira S, Blasco-Ibáñez J M, Crespo C, Pastor A M, Nacher J (2011). PSA-NCAM is Expressed in Immature, but not Recently Generated, Neurons in the Adult Cat Cerebral Cortex Layer II. Front Neurosci, 5: 17PubMedPubMedCentralCrossRefGoogle Scholar
  133. Varea E, Castillo-Gómez E, Gómez-Climent M A, Blasco-Ibáñez J M, Crespo C, Martínez-Guijarro F J, Nàcher J (2007).PSA-NCAM expression in the human prefrontal cortex. J Chem Neuroanat, 33(4): 202–209Google Scholar
  134. Varea E, Castillo-Gómez E, Gómez-Climent M A, Guirado R, Blasco-Ibáñez J M, Crespo C, Martínez-Guijarro F J, Nácher J (2009). Differential evolution of PSA-NCAM expression during aging of the rat telencephalon. Neurobiol Aging, 30(5): 808–818PubMedCrossRefGoogle Scholar
  135. Vessal M, Aycock A, Garton M T, Ciferri M, Darian-Smith C (2007). Adult neurogenesis in primate and rodent spinal cord: comparing a cervical dorsal rhizotomy with a dorsal column transection. Eur J Neurosci, 26(10): 2777–2794PubMedCrossRefGoogle Scholar
  136. Vivar C, van Praag H (2013). Functional circuits of new neurons in the dentate gyrus. Front Neural Circuits, 7: 15PubMedPubMedCentralCrossRefGoogle Scholar
  137. Winner B, Cooper-Kuhn C M, Aigner R, Winkler J, Kuhn H G (2002). Long-term survival and cell death of newly generated neurons in the adult rat olfactory bulb. Eur J Neurosci, 16(9): 1681–1689PubMedCrossRefGoogle Scholar
  138. Xiong K, Cai Y, Zhang X M, Huang J F, Liu Z Y, Fu G M, Feng J C, Clough RW, Patrylo P R, Luo X G, Hu C H, Yan X X (2010). Layer I as a putative neurogenic niche in young adult guinea pig cerebrum. Mol Cell Neurosci, 45(2): 180–191PubMedPubMedCentralCrossRefGoogle Scholar
  139. Xiong K, Luo D W, Patrylo P R, Luo X G, Struble R G, Clough R W, Yan X X (2008). Doublecortin-expressing cells are present in layer II across the adult guinea pig cerebral cortex: partial colocalization with mature interneuron markers. Exp Neurol, 211(1): 271–282PubMedPubMedCentralCrossRefGoogle Scholar
  140. Yang Y, Geldmacher D S, Herrup K (2001). DNA replication precedes neuronal cell death in Alzheimer’s disease. J Neurosci, 21(8): 2661–2668PubMedGoogle Scholar
  141. Yang Y, Xie M X, Li J M, Hu X, Patrylo P R, Luo X G, Cai Y, Li Z, Yan X X (2015). Prenatal genesis of layer II doublecortin expressing neurons in neonatal and young adult guinea pig cerebral cortex. Front Neuroanat, 9: 109PubMedPubMedCentralCrossRefGoogle Scholar
  142. Yuan T F, Liang Y X, So K F (2014). Occurrence of new neurons in the piriform cortex. Front Neuroanat, 8: 167PubMedGoogle Scholar
  143. Yuan T F, Liang Y X, So K F (2015). Response: New neurons from old beliefs in the adult piriform cortex? A Commentary on: “Occurrence of new neurons in the piriform cortex”. Front Neuroanat, 9: 79PubMedPubMedCentralGoogle Scholar
  144. Zhang J, Giesert F, Kloos K, Vogt Weisenhorn DM, Aigner L, Wurst W, Couillard-Despres S (2010). A powerful transgenic tool for fate mapping and functional analysis of newly generated neurons. BMC Neurosci, 11 (1): 158PubMedPubMedCentralCrossRefGoogle Scholar
  145. Zhang X M, Cai Y, Chu Y, Chen E Y, Feng J C, Luo X G, Xiong K, Struble R G, Clough R W, Patrylo P R, Kordower J H, Yan X X (2009). Doublecortin-expressing cells persist in the associative cerebral cortex and amygdala in aged nonhuman primates. Front Neuroanat, 3: 17PubMedPubMedCentralCrossRefGoogle Scholar
  146. Zhu X, Bergles D E, Nishiyama A (2008). NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development, 135(1): 145–157PubMedCrossRefGoogle Scholar
  147. Zhu X, Hill R A, Dietrich D, Komitova M, Suzuki R, Nishiyama A (2011). Age-dependent fate and lineage restriction of single NG2 cells. Development, 138(4): 745–753PubMedPubMedCentralCrossRefGoogle Scholar
  148. Zigova T, Betarbet R, Soteres B J, Brock S, Bakay R A, Luskin M B (1996). A comparison of the patterns of migration and the destinations of homotopically transplanted neonatal subventricular zone cells and heterotopically transplanted telencephalic ventricular zone cells. Dev Biol, 173(2): 459–474PubMedCrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Richard König
    • 1
    • 2
  • Bruno Benedetti
    • 3
  • Peter Rotheneichner
    • 1
    • 4
  • Anna O’ Sullivan
    • 1
    • 4
    • 5
  • Christina Kreutzer
    • 1
    • 4
  • Maria Belles
    • 6
  • Juan Nacher
    • 6
  • Thomas M. Weiger
    • 7
  • Ludwig Aigner
    • 1
    • 2
  • Sébastien Couillard-Després
    • 1
    • 4
  1. 1.Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS)Paracelsus Medical UniversitySalzburgAustria
  2. 2.Institute of Molecular Regenerative MedicineParacelsus Medical UniversitySalzburgAustria
  3. 3.Department of Physiology and Medical PhysicsInnsbruck Medical UniversityInnsbruckAustria
  4. 4.Institute of Experimental NeuroregenerationParacelsus Medical UniversitySalzburgAustria
  5. 5.Department of Otorhinolaryngology, Head and Neck SurgeryParacelsus Medical University SalzburgSalzburgAustria
  6. 6.Neurobiology Unit, Interdisciplinary Research Structure for Biotechnology and Biomedicine ValenciaUniversitat de ValenciaComunitat ValencianaSpain
  7. 7.Division of Cellular and Molecular Neurobiology, Department of Cell BiologyUniversity of SalzburgSalzburgAustria

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