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

Abstract

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.”

Key words： aging; cognition; doublecortin; piriform cortex; plasticity; neurogenesis

Acknowledgments

We would like to acknowledge Mr. Mark O′ Sullivan for his intellectual and literary input on this paper and Mag. Roman Fuchs for the images provided.

Compliance with ethics guidelines

Richard König, Bruno Benedetti, Peter Rotheneichner, Anna O’Sullivan, Christina Kreutzer, Maria Belles, Juan Nacher, M. Thomas Weiger, Ludwig Aigner, and Sébastien Couillard-Després declare that they have no conflicts of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

References

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): 285–292

PMID

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): 21–24

PMID

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): 1917–1924

PMID

4 Bekkers J M, Suzuki N (2013). Neurons and circuits for odor processing in the piriform cortex. Trends Neurosci, 36(7): 429–438

PMID

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): 11464–11469

PMID

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): 921–930

PMID

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): 17–20

PMID

8 Bizon J L, Gallagher M (2005). More is less: neurogenesis and age-related cognitive decline in Long-Evans rats. Sci SAGE KE, 2005(7): re2

PMID

9 Bizon J L, Lee H J, Gallagher M (2004). Neurogenesis in a rat model of age-related cognitive decline. Aging Cell, 3(4): 227–234

PMID

10 Bloch J, Kaeser M, Sadeghi Y, Rouiller E M, Redmond D EJr, 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): 775–789

PMID

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): 333–340

PMID

12 Bonfanti L (2013).The (real) neurogenic/gliogenic potential of the postnatal and adult brain parenchyma. ISRN Neurosci, 2013: 354136

PMID

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): 1–15

PMID

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): 419–436

PMID

15 Bonfanti L, Peretto P (2011). Adult neurogenesis in mammals—a theme with many variations. Eur J Neurosci, 34(6): 930–950

PMID

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): 612–627

PMID

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): 2042–2046

PMID

18 Burns K A, Ayoub A E, Breunig J J, Adhami F, Weng W L, Colbert M C, Rakic P, Kuan C Y (2007). Nestin-CreER mice reveal DNA synthesis by nonapoptotic neurons following cerebral ischemia hypoxia. Cereb Cortex, 17(11): 2585–2592

PMID

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 M R, Garcia-Verdugo J M, Prósper F, Low W C, 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): 1121–1127

PMID

20 Butt A M, Hamilton N, Hubbard P, Pugh M, Ibrahim M (2005). Synantocytes: the fifth element. J Anat, 207(6): 695–706

PMID

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): 342–356

PMID

22 Cameron H A, McKay R D (1999). Restoring production of hippocampal neurons in old age. Nat Neurosci, 2(10): 894–897

PMID

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): 507–518

PMID

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): 8173–8185

PMID

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): 11376–11388

PMID

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): 1535–1545

PMID

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): 1–14

PMID

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): 528–532

PMID

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): 476–488

PMID

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): 415–427

PMID

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): 961–970

PMID

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): 290–300

PMID

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): e9

PMID

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): 51–61

PMID

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): 10434–10442

PMID

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): 123–136

PMID

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): 9372–9382

PMID

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): 5046–5061

PMID

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): 15205–15217

PMID

40 Ehninger D, Kempermann G (2008). Neurogenesis in the adult hippocampus. Cell Tissue Res, 331(1): 243–250

PMID

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): 69–86

PMID

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): 308–328

PMID

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): 566–579

PMID

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): 247–251

PMID

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): 1313–1317

PMID

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): 1072–1083

PMID

47 Feliciano D M, Bordey A (2013). Newborn cortical neurons: only for neonates? Trends Neurosci, 36(1): 51–61

PMID

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): a018846

PMID

49 Fox G B, Fichera G, Barry T, O’Connell A W, 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): 135–141

PMID

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): 247–256

PMID

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): 3875–3883

PMID

52 Gage F H, Kempermann G, Song H (2008). Adult Neurogenesis, Vol 52. Cold Spring Harbor Laboratory Press

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): 589–593

PMID

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): 2229–2240

PMID

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): 159–172

PMID

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): 467–479

PMID

57 Gould E (2007).How widespread is adult neurogenesis in mammals? Nat Rev Neurosci, 8(6): 481–488

PMID

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): 186–192

PMID

59 Gritti A, Vescovi A L, Galli R (2002). Adult neural stem cells: plasticity and developmental potential. J Physiol Paris, 96(1-2): 81–90

PMID

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): 12036–12049

PMID

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): 146–154

PMID

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: 101–112

PMID

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): 223–233

PMID

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): 137–145

PMID

65 Kadohisa M, Wilson D A (2006a). Olfactory cortical adaptation facilitates detection of odors against background. J Neurophysiol, 95(3): 1888–1896

PMID

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): 15206–15211

PMID

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): 668–681

PMID

68 Kaplan M S (1981). Neurogenesis in the 3-month-old rat visual cortex. J Comp Neurol, 195(2): 323–338

PMID

69 Kapur A, Pearce R A, Lytton W W, Haberly L B (1997). GABAA-mediated IPSCs in piriform cortex have fast and slow components with different properties and locations on pyramidal cells. J Neurophysiol, 78(5): 2531–2545

PMID

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): 876–879

PMID

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): e300

PMID

72 Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004). Milestones of neuronal development in the adult hippocampus. Trends Neurosci, 27(8): 447–452

PMID

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): e25760

PMID

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): 702–716

PMID

75 König R, Rotheneichner P, Marschallinger J, Aigner L, Couillard-Despres S (2016). Adult Neurogenesis in the Hippocampus. Elsevier, pp. 145–176

76 Kornack D R, Rakic P (2001). Cell proliferation without neurogenesis in adult primate neocortex. Science, 294(5549): 2127–2130

PMID

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): e59269

PMID

78 Kuan C Y, Schloemer A J, Lu A, Burns K A, Weng W 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): 10763–10772

PMID

79 Kunz B A, Kohalmi S E (1991). Modulation of mutagenesis by deoxyribonucleotide levels. Annu Rev Genet, 25(1): 339–359

PMID

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): 313–328

PMID

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): 11032–11037

PMID

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): 695–714

PMID

83 Luzzati F, Bonfanti L, Fasolo A, Peretto P (2009). DCX and PSA-NCAM expression identifies a population of neurons preferentially distributed in associative areas of different pallial derivatives and vertebrate species. Cereb Cortex, 19(5): 1028–1041

PMID

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): 4065–4075

PMID

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): 13036–13041

PMID

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): 980–985

PMID

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): 449–460

PMID

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): 10–22

PMID

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): 923–934

PMID

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): 704–714

PMID

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: 62

PMID

92 Nacher J, Crespo C, McEwen B S (2001). Doublecortin expression in the adult rat telencephalon. Eur J Neurosci, 14(4): 629–644

PMID

93 Nacher J, Lanuza E, McEwen B S (2002). Distribution of PSA-NCAM expression in the amygdala of the adult rat. Neuroscience, 113(3): 479–484

PMID

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): 3921–3930

PMID

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): 99–106

PMID

96 Nishiyama A, Komitova M, Suzuki R, Zhu X (2009). Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci, 10(1): 9–22

PMID

97 Nishiyama A, Suzuki R, Zhu X (2014). NG2 cells (polydendrocytes) in brain physiology and repair. Front Neurosci, 8: 133

PMID

98 Nowakowski R S, Hayes N L (2000). New neurons: extraordinary evidence or extraordinary conclusion? Science, 288(5467): 771

PMID

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): 311–318

PMID

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): 3546–3553

PMID

101 Patzke N, LeRoy 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): 227–241

PMID

102 Peretto P, Bonfanti L (2014). Major unsolved points in adult neurogenesis: doors open on a translational future? Front Neurosci, 8: 154

PMID

103 Petreanu L, Alvarez-Buylla A (2002). Maturation and death of adult-born olfactory bulb granule neurons: role of olfaction. J Neurosci, 22(14): 6106–6113

PMID

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): 723–730

PMID

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): 57–67

PMID

106 Purves D, Augustine G J, Flitzpatrick D, Katz L C, LaMantia A S, McNamara J O, Williams S M (2001). Neuroscience, 2nd edition. Sunderland (MA): Sinauer Associates

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): 661–673

PMID

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): 1392–1401

PMID

109 Robins S C, Trudel E, Rotondi O, Liu X, Djogo T, Kryzskaya D, Bourque C W, Kokoeva M V (2013). Evidence for NG2-glia derived, adult-born functional neurons in the hypothalamus. PLoS ONE, 8(10): e78236

PMID

110 Rosselli-Austin L, Altman J (1979). The postnatal development of the main olfactory bulb of the rat. J Dev Physiol, 1(4): 295–313

PMID

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): 1006–1012

PMID

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.22357

PMID

113 Rutishauser U (2008). Polysialic acid in the plasticity of the developing and adult vertebrate nervous system. Nat Rev Neurosci, 9(1): 26–35

PMID

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 amygdaloid-kindling-induced sprouting of a hippocampal mossy fiber trajectory. Neurosci Res, 48(2): 185–194

PMID

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): 368–374

PMID

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): 382–386

PMID

117 Seki T, Arai Y (1999). Temporal and spacial relationships between PSA-NCAM-expressing, newly generated granule cells, and radial glia-like cells in the adult dentate gyrus. J Comp Neurol, 410(3): 503–513

PMID

118 Shapiro L A, Ng K, Zhou Q Y, Ribak C E (2009). Subventricular zone-derived, newly generated neurons populate several olfactory and limbic forebrain regions. Epilepsy Behav, 14(Suppl 1): 74–80

PMID

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): 133–148

PMID

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): 981–985

PMID

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): 2277–2282

PMID

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): 372–376

PMID

123 Shors T J, Townsend D A, Zhao M, Kozorovitskiy Y, Gould E (2002). Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus, 12(5): 578–584

PMID

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): 1219–1227

PMID

125 Suzuki N, Bekkers J M (2007). Inhibitory interneurons in the piriform cortex. Clin Exp Pharmacol Physiol, 34(10): 1064–1069

PMID

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): 2971–2984

PMID

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): 1670–1687

PMID

128 Takemura N U (2005). Evidence for neurogenesis within the white matter beneath the temporal neocortex of the adult rat brain. Neuroscience, 134(1): 121–132

PMID

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): 901–907

PMID

130 Toni N, Teng E M, 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): 727–734

PMID

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): 1030–1034

PMID

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: 17

PMID

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): 202–209

PMID

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): 808–818

PMID

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): 2777–2794

PMID

136 Vivar C, van Praag H (2013). Functional circuits of new neurons in the dentate gyrus. Front Neural Circuits, 7: 15

PMID

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): 1681–1689

PMID

138 Xiong K, Cai Y, Zhang X M, Huang J F, Liu Z Y, Fu G M, Feng J C, Clough R W, 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): 180–191

PMID

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): 271–282

PMID

140 Yang Y, Geldmacher D S, Herrup K (2001). DNA replication precedes neuronal cell death in Alzheimer’s disease. J Neurosci, 21(8): 2661–2668

PMID

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: 109

PMID

142 Yuan T F, Liang Y X, So K F (2014). Occurrence of new neurons in the piriform cortex. Front Neuroanat, 8: 167

PMID

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: 79

PMID

144 Zhang J, Giesert F, Kloos K, Vogt Weisenhorn D M, 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): 158

PMID

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: 17

PMID

146 Zhu X, Bergles D E, Nishiyama A (2008). NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development, 135(1): 145–157

PMID

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): 745–753

PMID

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): 459–474

PMID