Dopamine Systems in the Forebrain

  • John W. Cave
  • Harriet BakerEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 651)


The brain contains a number of distinct regions that share expression of dopamine (DA) and its requisite biosynthetic machinery, but otherwise encompass a diverse array of features and functions. Across the vertebrate family, the olfactory bulb (OB) contains the major DA system in the forebrain. OB DA cells are primarily periglomerular interneurons that define the glomerular structures in which they receive innervation from olfactory receptor neurons as well as mitral and tufted cells, the primary OB output neurons. The OB DA cells are necessary for both discrimination and the dynamic range over which odorant sensory information can be detected. In the embryo, OB DA neurons are derived from the ventricular area of the evaginating telencephalon, the dorsal lateral ganglionic eminence and the septum. However, most OB DA interneurons are generated postnatally and continue to be produced throughout adult life from neural stem cells in the subventricular zone of the lateral ventricle and rostral migratory stream. Adult born OB DA neurons are capable of integrating into existing circuits and do not appear to degenerate in Parkinson’s disease. Several genes have been identified that regulate the differentiation of OB DA interneurons from neural stem cells. These include transcription factors that modify the expression of tyrosine hydroxylase, the first enzyme in the DA biosynthetic pathway and a reliable marker of the DA phenotype. Elucidation of the molecular genetic pathways of OB DA differentiation may advance the development of strategies to treat neurological disease.


Tyrosine Hydroxylase Olfactory Bulb Neural Stem Cell Subventricular Zone Olfactory Receptor Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hornykiewicz O. Parkinson’s disease: from brain homogenate to treatment. Fed Proc 1973; 32(2):183–190.PubMedGoogle Scholar
  2. 2.
    Baker H, Kawano T, Margolis FL et al. Transneuronal regulation of tyrosine hydroxylase expression in olfactory bulb of mouse and rat. J Neurosci 1983; 3:69–78.PubMedGoogle Scholar
  3. 3.
    Wilson DA, Sullivan RM. The D2 antagonist spiperone mimics the effects of olfactory deprivation on mitral/tufted cell odor response patterns. J Neurosci 1995; 15(8):5574–5581.PubMedGoogle Scholar
  4. 4.
    Wilson DA, Wood JG. Functional consequences of unilateral olfactory deprivation: time course and age sensitivity. Neurosci 1992; 49:183–192.CrossRefGoogle Scholar
  5. 5.
    Lledo PM, Alonso M, Grubb MS. Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 2006; 7(3):179–193.PubMedCrossRefGoogle Scholar
  6. 6.
    Lledo PM, Saghatelyan A, Lemasson M. Inhibitory interneurons in the olfactory bulb: from development to function. Neuroscientist 2004; 10(4):292–303.PubMedCrossRefGoogle Scholar
  7. 7.
    Luskin MB. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 1993; 11:173–189.PubMedCrossRefGoogle Scholar
  8. 8.
    Huisman E, Uylings HB, Hoogland PV. A 100% increase of dopaminergic cells in the olfactory bulb may explain hyposmia in Parkinson’s disease. Mov Disord 2004; 19(6):687–692.PubMedCrossRefGoogle Scholar
  9. 9.
    Halasz N, Hokfelt T, Ljungdahl A et al. Dopamine neurons in the olfactory bulb. Adv Biochem Psychopharmacol 1977; 16:169–177.PubMedGoogle Scholar
  10. 10.
    Lidbrink P, Jonsson G, Fuxe K. Selective reserpine-resistant accumulation of catecholamines in central dopamine neurones after DOPA administration. Brain Res 1974; 67(3):439–456.PubMedCrossRefGoogle Scholar
  11. 11.
    Lledo PM, Saghatelyan A. Integrating new neurons into the adult olfactory bulb: joining the network, life-death decisions and the effects of sensory experience. Trends Neurosci 2005; 28(5):248–254.PubMedCrossRefGoogle Scholar
  12. 12.
    Marin O, Rubenstein JL. A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci 2001; 2(11):780–790.PubMedCrossRefGoogle Scholar
  13. 13.
    Wonders CP, Anderson SA. The origin and specification of cortical interneurons. Nat Rev Neurosci 2006; 7(9):687–696.PubMedCrossRefGoogle Scholar
  14. 14.
    Gheusi G, Cremer H, McLean H et al. Importance of newly generated neurons in the adult olfactory bulb for odor discrimination. Proc Natl Acad Sci USA 2000; 97(4):1823–1828.PubMedCrossRefGoogle Scholar
  15. 15.
    Gheusi G, Lledo PM. Control of early events in olfactory processing by adult neurogenesis. Chem Senses 2007; 32(4):397–409.PubMedCrossRefGoogle Scholar
  16. 16.
    Hack MA, Saghatelyan A, de Chevigny A et al. Neuronal fate determinants of adult olfactory bulb neurogenesis. Nat Neurosci 2005; 8(7):865–872.PubMedGoogle Scholar
  17. 17.
    Ortega-Perez I, Murray K, Lledo PM. The how and why of adult neurogenesis. J Mol Histol 2007; 99(6):555–562.CrossRefGoogle Scholar
  18. 18.
    Cossette M, Lecomte F, Parent A. Morphology and distribution of dopaminergic neurons intrinsic to the human striatum. J Chem Neuroanat 2005; 29(1):1–11.PubMedCrossRefGoogle Scholar
  19. 19.
    Cossette M, Levesque D, Parent A. Neurochemical characterization of dopaminergic neurons in human striatum. Parkinsonism Relat Disord 2005; 11(5):277–286.PubMedCrossRefGoogle Scholar
  20. 20.
    Farbman AI. Cell Biology of Olfaction. New York: Cambridge University Press, 1992.Google Scholar
  21. 21.
    Baker H, Farbman AI. Olfactory afferent regulation of the dopamine phenotype in the fetal rat olfactory system. Neurosci 1993; 52:115–134.CrossRefGoogle Scholar
  22. 22.
    Baker H, Morel K, Stone DM et al. Adult naris closure profoundly reduces tyrosine hydroxylase expression in mouse olfactory bulb. Brain Res 1993; 614:109–116.PubMedCrossRefGoogle Scholar
  23. 23.
    Kosaka K, Aika Y, Toida K et al. Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb. Neurosci Res 1995; 23(1):73–88.PubMedGoogle Scholar
  24. 24.
    De Marchis S, Bovetti S, Carletti B et al. Generation of distinct types of periglomerular olfactory bulb interneurons during development and in adult mice: implication for intrinsic properties of the subventricular zone progenitor population. J Neurosci 2007; 27(3):657–664.PubMedCrossRefGoogle Scholar
  25. 25.
    Parrish-Aungst S, Shipley MT, Erdelyi F et al. Quantitative analysis of neuronal diversity in the mouse olfactory bulb. J Comp Neurol 2007; 501(6):825–836.PubMedCrossRefGoogle Scholar
  26. 26.
    Macrides F, Davis BJ, Youngs WM et al. Cholinergic and catecholaminergic afferents to the olfactory bulb in the hamster: a neuroanatomical, biochemical and histochemical investigation. J Comp Neurol 1981; 203(3):495–514.PubMedCrossRefGoogle Scholar
  27. 27.
    McLean JH, Shipley MT. Serotonergic afferents to the rat olfactory bulb: II. Changes in fiber distribution during development. J Neurosci 1987; 7(10):3029–3039.PubMedGoogle Scholar
  28. 28.
    McLean JH, Shipley MT. Serotonergic afferents to the rat olfactory bulb: I. Origins and laminar specificity of serotonergic inputs in the adult rat. J Neurosci 1987; 7(10):3016–3028.PubMedGoogle Scholar
  29. 29.
    Kasowski HJ, Kim H, Greer CA. Compartmental organization of the olfactory bulb glomerulus. J Comp Neurol 1999; 407(2):261–274.PubMedCrossRefGoogle Scholar
  30. 30.
    White EL. Synaptic organization of the mammalian olfactory glomerulus: new findings including an intraspecific variation. Brain Res 1973; 60(2):299–313.PubMedCrossRefGoogle Scholar
  31. 31.
    Kosaka K, Toida K, Aika Y et al. How simple is the organization of the olfactory glomerulus? The heterogeneity of so-called periglomerular cells. Neurosci Res 1998; 30(2):101–110.PubMedCrossRefGoogle Scholar
  32. 32.
    Toida K, Kosaka K, Aika Y et al. Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb—IV. Intraglomerular synapses of tyrosine hydroxylase-immunoreactive neurons. Neuroscience 2000; 101(1):11–17.PubMedCrossRefGoogle Scholar
  33. 33.
    Nagatsu T, Levitt M, Udenfriend S. Tyrosine hydroxylase: The initial step in norepinephrine biosynthesis. J Biol Chem 1964; 239:2910–2917.PubMedGoogle Scholar
  34. 34.
    Joh TH, Geghman C, Reis DJ. Immunochemical demonstration of increased accumulation of TH protein in sympathetic ganglia and adrenal medulla elicited by reserpine. J Neurochem 1973; 39:342–348.Google Scholar
  35. 35.
    McLean JH, Shipley MT. Postnatal development of the noradrenergic projection from locus coeruleus to the olfactory bulb in the rat. J Comp Neurol 1991; 304(3):467–477.PubMedCrossRefGoogle Scholar
  36. 36.
    Baker H, Abate C, Szabo A et al. Species specific distribution of aromatic 1-amino acid decarboxylase in rodent adrenal gland, cerebellum and olfactory bulb. J Comp Neurol 1991; 305:119–129.PubMedCrossRefGoogle Scholar
  37. 37.
    Cerruti C, Walther DM, Kuhar MJ et al. Dopamine transporter mRNA expression is intense in rat midbrain neurons and modest outside midbrain. Brain Res Mol Brain Res 1993; 18(1–2):181–186.PubMedCrossRefGoogle Scholar
  38. 38.
    Coronas V, Srivastava LK, Liang JJ et al. Identification and localization of dopamine receptor subtypes in rat olfactory mucosa and bulb: a combined in situ hybridization of ligand binding radioautographic approach. J Chem Neuroanat 1997; 12(4):243–257.PubMedCrossRefGoogle Scholar
  39. 39.
    Koster NL, Norman AB, Richtand NM et al. Olfactory receptor neurons express D2 dopamine receptors. J Comp Neurol 1999; 411(4):666–673.PubMedCrossRefGoogle Scholar
  40. 40.
    Meador-Woodruff JH, Mansour A, Bunzow JR et al. Distribution of D2 dopamine receptor mRNA in rat brain. Proc Natl Acad Sci USA 1989; 86(19):7625–7628.PubMedCrossRefGoogle Scholar
  41. 41.
    Baker H. Unilateral, neonatal olfactory deprivation alters tyrosine hydroxylase expression but not aromatic amino acid decarboxylase or GABA immunoreactivity. Neurosci 1990; 36:761–771.CrossRefGoogle Scholar
  42. 42.
    Baker H, Cummings DM, Munger SD et al. Targeted deletion of a cyclic nucleotide-gated channel subunit (OCNC1): Biochemical and morphological consequences in adult mice. J Neurosci 1999; 19:9313–9321.PubMedGoogle Scholar
  43. 43.
    Philpot BD, Men D, McCarty R et al. Activity-dependent regulation of dopamine content in the olfactory bulbs of naris-occluded rats. Neuroscience 1998; 85(3):969–977.PubMedCrossRefGoogle Scholar
  44. 44.
    Guthrie KM, Pullara JM, Marshall JF et al. Olfactory deprivation increases dopamine D2 receptor density in the rat olfactory bulb. Synapse 1991; 8:61–70.PubMedCrossRefGoogle Scholar
  45. 45.
    Gall CM, Hendry SCH, Seroogy KB et al. Evidence for co-existence of GABA and dopamine in neurons of the rat olfactory bulb. J Comp Neurol 1987; 266:307–318.PubMedCrossRefGoogle Scholar
  46. 46.
    Waclaw RR, Allen ZJ 2nd, Bell SM et al. The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons. Neuron 2006; 49(4):503–516.PubMedCrossRefGoogle Scholar
  47. 47.
    Brunig I, Sommer M, Hatt H et al. Dopamine receptor subtypes modulate olfactory bulb gamma-aminobutyric acid type A receptors. Proc Natl Acad Sci USA 1999; 96(5):2456–2460.PubMedCrossRefGoogle Scholar
  48. 48.
    Aroniadou-Anderjaska V, Ennis M, Shepley MT. Glomerular synaptic responses to olfactory nerve input in rat olfactory bulb slices. Neuroscience 1997; 79(2):425–434.PubMedCrossRefGoogle Scholar
  49. 49.
    Berkowicz DA, Trombley PQ, Shepherd GM. Evidence for glutamate as the olfactory receptor cell neurotransmitter. J Neurophysiol 1994; 71(6):2557–2561.PubMedGoogle Scholar
  50. 50.
    Ennis M, Zimmer LA, Shipley MT: Olfactory nerve stimulation activates rat mitral cells via NMDA and non NMDA receptors in vitro [see comments]. Neuroreport 1996; 7(5):989–992.PubMedGoogle Scholar
  51. 51.
    Ennis M, Zhou FM, Ciombor KJ et al. Dopamine D2 receptor-mediated presynaptic inhibition of olfactory nerve terminals. J Neurophysiol 2001; 86(6):2986–2997.PubMedGoogle Scholar
  52. 52.
    Aroniadou-Anderjaska V, Zhou FM, Priest CA et al. Tonic and synaptically evoked presynaptic inhibition of sensory input to the rat olfactory bulb via GABA(B) heteroreceptors. J Neurophysiol 2000; 84(3):1194–1203.PubMedGoogle Scholar
  53. 53.
    Keller A, Yagodin S, Aroniadou-Anderjaska V et al. Functional organization of rat olfactory bulb glomeruli revealed by optical imaging. J Neurosci 1998; 18(7):2602–2612.PubMedGoogle Scholar
  54. 54.
    Murphy GJ, Glickfeld LL, Balsen Z et al. Sensory neuron signaling to the brain: properties of transmitter release from olfactory nerve terminals. J Neurosci 2004; 24(12):3023–3030.PubMedCrossRefGoogle Scholar
  55. 55.
    Palouzier-Paulignan B, Duchamp-Viret P, Hardy AB et al. GABA(B) receptor-mediated inhibition of mitral/tufted cell activity in the rat olfactory bulb: a whole-cell patch-clamp study in vitro. Neuroscience 2002; 111(2):241–250.PubMedCrossRefGoogle Scholar
  56. 56.
    Murphy GJ, Darcy DP, Isaacson JS. Intraglomerular inhibition: signaling mechanisms of an olfactory microcircuit. Nat Neurosci 2005; 8(3):354–364.PubMedCrossRefGoogle Scholar
  57. 57.
    Smith TC, Jahr CE. Self-inhibition of olfactory bulb neurons. Nat Neurosci 2002; 5(8):760–766.PubMedGoogle Scholar
  58. 58.
    Berkowicz DA, Trombley PQ. Dopaminergic modulation at the olfactory nerve synapse. Brain Res 2000; 855(1):90–99.PubMedCrossRefGoogle Scholar
  59. 59.
    Hsia AY, Vincent JD, Lledo PM. Dopamine depresses synaptic inputs into the olfactory bulb. J Neurophysiol 1999; 82(2):1082–1085.PubMedGoogle Scholar
  60. 60.
    Davila NG, Blakemore LJ, Trombley PQ. Dopamine modulates synaptic transmission between rat olfactory bulb neurons in culture. J Neurophysiol 2003; 90(1):395–404.PubMedCrossRefGoogle Scholar
  61. 61.
    Gutierrez-Mecinas M, Crespo C, Blasco-Ibanez JM et al. Distribution of D2 dopamine receptor in the olfactory glomeruli of the rat olfactory bulb. Eur J Neurosci 2005; 22(6):1357–1367.PubMedCrossRefGoogle Scholar
  62. 62.
    Davison IG, Boyd JD, Delaney KR. Dopamine inhibits mitral/tufted→ granule cell synapses in the frog olfactory bulb. J Neurosci 2004; 24(37):8057–8067.PubMedCrossRefGoogle Scholar
  63. 63.
    Baker H, Towle AC, Margolis FL. Differential afferent regulation of the dopamine and gabaergic systems of the mouse main olfactory bulb. Brain Res 1988; 450:69–80.PubMedCrossRefGoogle Scholar
  64. 64.
    Stone DM, Grillo M, Margolis FL et al. Differential effect of functional olfactory bulb deafferentation on tyrosine hydroxylase and glutamic acid decarboxylase messenger RNA levels in rodent juxtaglomerular neurons. J Comp Neurol 1991; 311:223–233.PubMedCrossRefGoogle Scholar
  65. 65.
    Hinds JW. Autoradiographic study of histogenesis in the mouse olfactory bulb. I. Time of origin of neurons and neuroglia. J Comp Neurol 1968; 134(3):287–304.PubMedCrossRefGoogle Scholar
  66. 66.
    Stenman J, Toresson H, Campbell K. Identification of two distinct progenitor populations in the lateral ganglionic eminence: implications for striatal and olfactory bulb neurogenesis. J Neurosci 2003; 23(1):167–174.PubMedGoogle Scholar
  67. 67.
    Yun K, Garel S, Fischman S et al. Patterning of the lateral ganglionic eminence by the Gsh1 and Gsh2 homeobox genes regulates striatal and olfactory bulb histogenesis and the growth of axons through the basal ganglia. J Comp Neurol 2003; 461(2):151–165.PubMedCrossRefGoogle Scholar
  68. 68.
    Lois C, Garcia-Verdugo JM, Alvarez-Buylla A. Chain migration of neuronal precursors. Science 1996; 271(5251):978–981.PubMedCrossRefGoogle Scholar
  69. 69.
    Luskin MB, Zigova T, Soteres BJ et al. Neuronal progenitor cells derived from the anterior subventricular zone of the neonatal rat forebrain continue to proliferate in vitro and express a neuronal phenotype. Mol and Cell Neurosci 1997; 8:351–366.CrossRefGoogle Scholar
  70. 70.
    Vergano-Vera E, Yusta-Boyo MJ, de Castro F et al. Generation of GABAergic and dopaminergic interneurons from endogenous embryonic olfactory bulb precursor cells. Development 2006; 133(21):4367–4379.PubMedCrossRefGoogle Scholar
  71. 71.
    Inoue T, Ota M, Ogawa M et al. Zic1 and Zic3 regulate medial forebrain development through expansion of neuronal progenitors. J Neurosci 2007; 27(20):5461–5473.PubMedCrossRefGoogle Scholar
  72. 72.
    Altman J, Das GD. Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions. J Comp Neurol 1966; 126(3):337–389.PubMedCrossRefGoogle Scholar
  73. 73.
    Bayer SA. [3H] Thymidine-radiographic studies of neurogenesis in the rat olfactory bulb. Exp Brain Res 1983; 50:329–340.PubMedCrossRefGoogle Scholar
  74. 74.
    Bulfone A, Kim HJ, Puelles L et al. The mouse Dlx-2 (Tes-1) gene is expressed in spatially restricted domains of the forebrain, face and limbs in midgestation mouse embryos. Mech Dev 1993; 40(3):129–140.PubMedCrossRefGoogle Scholar
  75. 75.
    Long JE, Garel S, Depew MJ et al. DLX5 regulates development of peripheral and central components of the olfactory system. J Neurosci 2003; 23(2):568–578.PubMedGoogle Scholar
  76. 76.
    Porteus MH, Bulfone A, Liu JK et al. DLX-2, MASH-1 and MAP-2 expression and bromodeoxyuridine incorporation define molecularly distincT-cell populations in the embryonic mouse forebrain. J Neurosci 1994;14(11 Pt 1):6370–6383.PubMedGoogle Scholar
  77. 77.
    Saino-Saito S, Cave JW, Akiba Y et al. ER81 and CaMKIV identify anatomically and phenotypically defined subsets of mouse olfactory bulb interneurons. J Comp Neurol 2007;502(4):485–496.PubMedCrossRefGoogle Scholar
  78. 78.
    Stoykova A, Gruss P. Roles of Pax-genes in developing and adult brain as suggested by expression patterns. J Neurosci 1994;14(3 Pt 2):1395–1412.PubMedGoogle Scholar
  79. 79.
    Toresson H, Campbell K. A role for Gsh1 in the developing striatum and olfactory bulb of Gsh2 mutant mice. Development 2001;128(23):4769–4780.PubMedGoogle Scholar
  80. 80.
    Curtis MA, Kam M, Nannmark U et al. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 2007;315(5816):1243–1249.PubMedCrossRefGoogle Scholar
  81. 81.
    Doetsch F. The glial identity of neural stem cells. Nat Neurosci 2003;6(11):1127–1134.PubMedCrossRefGoogle Scholar
  82. 82.
    Doetsch F. A niche for adult neural stem cells. Curr Opin Genet Dev 2003:13(5):543–550.PubMedCrossRefGoogle Scholar
  83. 83.
    Merkle FT, Alvarez-Buylla A. Neural stem cells in mammalian development. Curr Opin Cell Biol 2006; 18(6):704–709.PubMedCrossRefGoogle Scholar
  84. 84.
    Luskin MB, Coskun V. The progenitor cells of the embryonic telencephalon and the neonatal anterior subventricular zone differentially regulate their cell cycle. Chem Senses 2002;27(6):577–580.PubMedCrossRefGoogle Scholar
  85. 85.
    Young KM, Fogarty M, Kessaris M et al. Subventricular zone stem cells are heterogeneous with respect to their embryonic origins and neurogenic fates in the adult olfactory bulb. J Neurosci 2007; 27(31):8286–8296.PubMedCrossRefGoogle Scholar
  86. 86.
    Merkle FT, Mirzadeh Z, Alvarez-Buylla A. Mosaic organization of neural stem cells in the adult brain. Science 2007;317(5836):381–384.PubMedCrossRefGoogle Scholar
  87. 87.
    Dellovade TL, Pfaff DW. Schwanzel-Fukuda M. Olfactory bulb development is altered in small-eye (Sey) mice. J Comp Neurol 1998;402(3):402–418.PubMedCrossRefGoogle Scholar
  88. 88.
    Kohwi M, Osumi N, Rubensstein JL et al. Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb. J Neurosci 2005;25(30):6997–7003.PubMedCrossRefGoogle Scholar
  89. 89.
    Stoykova A, Fritsch R, Walther C et al. Forebrain patterning defects in Small eye mutant mice. Development 1996;122(11):3453–3465.PubMedGoogle Scholar
  90. 90.
    Allen ZJ 2nd, Waclaw RR, Colbert MC et al. Molecular identity of olfactory bulb interneurons: transcriptional codes of periglomerular neuron subtypes. J Mol Histol 2007;38(6):517–525.PubMedCrossRefGoogle Scholar
  91. 91.
    Doetsch F, Petreanu L, Caille I et al. EGF converts transit-amplifying neurogenic precursors inthe adult brain into multipotent stem cells. Neuron 2002;36(6):1021–1034.PubMedCrossRefGoogle Scholar
  92. 92.
    Kohwi M, Petryniak MA, Long, JE et al. A subpopulation of olfactory bulb GABAergic interneurons is derived from Emxl-and Dlx5/6-expressing progenitors. J Neurosci 2007;27(26):6878–6891.PubMedCrossRefGoogle Scholar
  93. 93.
    Saino-Saito S, Sasaki H, Volpe BT et al. Differentiation of the dopaminergic phenotype in the olfactory system of neonatal and adult mice. J Comp Neurol 2004;479(4):389–398.PubMedCrossRefGoogle Scholar
  94. 94.
    Baker H, Liu N, Chun HS et al. Phenotypic differentiation during migration of dopaminergic progenitor cells to the olfactory bulb. J Neurosci 2001;21(21):8505–8513.PubMedGoogle Scholar
  95. 95.
    Schimmel JJ, Crews J, Roffler-Tarlov S et al. 4.5 kb of the rat tyrosine hydroxylase 5′ flanking sequence directs tissue specific expression during development and contains consensus sites for multiple transcription factors. Brain Res Mol Brain Res 1999;74(1–2):1–4.PubMedCrossRefGoogle Scholar
  96. 96.
    Baker H, Kobayashi K, Okano H et al. Cortical and striatal expression of tyrosine hydroxylase mRNA in neonatal and adult mice. Cell Mol Neurobiol 2003;23(4–5):507–518.PubMedCrossRefGoogle Scholar
  97. 97.
    Anderson SA, Marin O, Horn C et al. Distinct cortical migrations from the medial and lateral ganglionic eminences. Development 2001 128(3):353–363.PubMedGoogle Scholar
  98. 98.
    Wichterle H, Turnbull DH, Nery S et al. In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain. Development 2001;128(19):3759–3771.PubMedGoogle Scholar
  99. 99.
    Chi N, Epstein JA. Getting your Pax straight: Pax proteins in development and disease. Trends Genet 2002;18(1):41–47.PubMedCrossRefGoogle Scholar
  100. 100.
    Czerny T, Busslinger M. DNA-binding and transactivation properties of Pax-6: three amino acids in the paired domain are responsible for the different sequence recognition of Pax-6 and BSAP (Pax-5). Mol Cell Biol 1995;15(5):2858–2871.PubMedGoogle Scholar
  101. 101.
    Epstein JA, Glaser T, Cai J et al. Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing. Genes Dev 1994;8(17):2022–2034.PubMedCrossRefGoogle Scholar
  102. 102.
    Kozmik Z, Czermy T, Busslinger M. Alternatively spliced insertions in the paired domain restrict the DNA sequence specificity of Pax6 and Pax8. Embo J 1997;16(22):6793–6803.PubMedCrossRefGoogle Scholar
  103. 103.
    Mishra R, Gorlov IP, Chap LY et al. PAX6, paired domain influences sequence recognition by the homeodomain. J Biol Chem 2002;277(51):49488–49494.PubMedCrossRefGoogle Scholar
  104. 104.
    Caric D, Gooday D, Hill RE et al. Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6. Development 1997;124(24):5087–5096.PubMedGoogle Scholar
  105. 105.
    Haubst N, Berget J, Radjendirane V et al. Molecular dissection of Pax6 function: the specific roles of the paired domain and homeodomain in brain development. Development 2004; 131(24):6131–6140.PubMedCrossRefGoogle Scholar
  106. 106.
    Quinn JC, Molinek M, Martynoga BS et al. Pax6 controls cerebral cortical cell number by regulating exit from the cell cycle and specifies cortical cell indentity by a cell autonomous mechanism. Dev Biol 2007; 302(1):50–65.PubMedCrossRefGoogle Scholar
  107. 107.
    Talamillo A, Quinn, JC, Collinson JM et al. Pax6 regulates development and neuronal migration in the cerebral cortex. Dev Biol 2003; 255(1):151–163.PubMedCrossRefGoogle Scholar
  108. 108.
    Liu N, Baker H. Activity-dependent Nurrl and NGFI-B gene expression in adult mouse olfactory bulb. Neuroreport 1999; 10(4):747–751.PubMedCrossRefGoogle Scholar
  109. 109.
    Zetterstrom RH, Williams R, Perlmann T et al. Cellular expression of the immediate early transcription factors Nurrl and NGFI-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system. Brain Res Mol Brain Res 1996; 41(1–2):111–120.PubMedCrossRefGoogle Scholar
  110. 110.
    Kim KS, Kim CH, Hwang DY et al. Orphan nuclear receptor Nurrl directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific manner. J Neurochem 2003; 85(3):622–634.PubMedCrossRefGoogle Scholar
  111. 111.
    Sakurada K, Ohshima-Sakurada M, Palmer TD et al. Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain. Development 1999; 126(18):4017–4026.PubMedGoogle Scholar
  112. 112.
    Le W, Conneely OM, Zou L et al. Selective agenesis of mesencephalic dopaminergic neurons in Nurr1-deficient mice. Exp Neurol 1999; 159(2):451–458.PubMedCrossRefGoogle Scholar
  113. 113.
    Zetterstrom RH, Solomin L, Jansson L et al. Dopamine neuron agenesis in Nurr1-deficient mice. Science 1997; 276:248–250.PubMedCrossRefGoogle Scholar
  114. 114.
    Fung BP, Yoon SO, Chikaraishi DM. Sequences that direct rat tyrosine hydroxylase gene expression. J Neurochem 1992; 58(6):2044–2052.PubMedCrossRefGoogle Scholar
  115. 115.
    Nagamoto-Combs K, Piech MK, Best JA et al. Tyrosine hydroxylase gene promoter activity is regulated by both cyclic AMP-responsive element and AP1 sites following calcium influx. Evidence for cyclic amp-responsive element binding protein-independent regulation. J Biol Chem 1997; 272(9):6051–6058.PubMedCrossRefGoogle Scholar
  116. 116.
    Trocme C, Sarkis C, Hermel JM et al. CRE and TRE sequences of the rat tyrosine hydroxylase promoter are required for TH basal expression in adult mice but not in the embryo. Eur J Neurosci 1998; 10(2):508–521.PubMedCrossRefGoogle Scholar
  117. 117.
    Liu N, Cigola E, Tinti C et al. Unique regulation of immediate early gene and tyrosine hydroxylase expression in the odor-deprived mouse olfactory bulb. J Biol Chem 1999; 274:3042–3047.PubMedCrossRefGoogle Scholar
  118. 118.
    Akiba Y, Sasaki H, Saino-Saito S et al. Temporal and spatial disparity in cFOS expression and dopamine phenotypic differentiation in the neonatal mouse olfactory bulb. Neurochem Res 2007; 32(4–5):625–634.PubMedCrossRefGoogle Scholar
  119. 119.
    Cigola E, Volpe BT, Lee JW et al. Tyrosine hydroxylase expression in primary cultures of olfactory bulb: role of L-type calcium channels. J Neurosci 1998; 18:7638–67649.PubMedGoogle Scholar
  120. 120.
    West AE, Chen WG, Dalva MB et al. Calcium regulation of neuronal gene expression. Proc Natl Acad Sci USA 2001; 98(20):11024–11031.PubMedCrossRefGoogle Scholar
  121. 121.
    Behar TN, Smith SV, Kennedy RT et al. GABA(B) receptors mediate motility signals for migrating embryonic cortical cells. Cereb Cortex 2001; 11(8):744–753.PubMedCrossRefGoogle Scholar
  122. 122.
    Bolteus AJ, Bordey A. GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone. J Neurosci 2004; 24(35):7623–7631.PubMedCrossRefGoogle Scholar
  123. 123.
    Cancedda L, Fiumelli H, Chen K et al. Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo. J Neurosci 2007; 27(19):5224–5235.PubMedCrossRefGoogle Scholar
  124. 124.
    Carleton A, Petreanu LT, Lansford R et al. Becoming a new neuron in the adult olfactory bulb. Nat Neurosci 2003; 6(5):507–518.PubMedGoogle Scholar
  125. 125.
    Gascon E, Dayer AG, Sauvain MO et al. GABA regulates dendritic growth by stabilizing lamellipodia in newly generated interneurons of the olfactory bulb. J Neurosci 2006; 26(50):12956–12966.PubMedCrossRefGoogle Scholar
  126. 126.
    Ge S, Pradhan DA, Ming GL et al. GABA sets the tempo for activity-dependent adult neurogenesis. Trends Neurosci 2007; 30(1):1–8.PubMedCrossRefGoogle Scholar
  127. 127.
    Chambers CB, Peng Y, Nguyen H et al. Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors. Development 2001; 128(5):689–702.PubMedGoogle Scholar
  128. 128.
    Yoshihara S, Omichi K, Yanazawa M et al. Arx homeobox gene is essential for development of mouse olfactory system. Development 2005; 132(4):751–762.PubMedCrossRefGoogle Scholar
  129. 129.
    Baker H, Cummings DM, Munger SD et al. Targeted deletion of a cyclic nucleotide-gated channel subunit (OCNC1): biochemical and morphological consequences in adult mice. J Neurosci 1999; 19(21):9313–9321.PubMedGoogle Scholar
  130. 130.
    Missale C, Nash SR, Robinson SW et al. Dopamine receptors: from structure to function. Physiol Rev 1998; 78(1):189–225.PubMedGoogle Scholar
  131. 131.
    Mansour A, Watson SJ Jr. Dopamine receptor expression in the central nervous system In: Bloom F, Kupfer D, eds. Pyschopharmacology: The Fourth Generation of Progress. New York City: Raven Press Ltd, 1995:207–219.Google Scholar
  132. 132.
    Mink J, Basal Ganglia. In: Zigmond M, Bloom F, Landis S, Roberts J, Squire L, eds. Fundamental Neuroscience. New York: Academic Press, 1999;951–972.Google Scholar
  133. 133.
    Fallon J, Loughlin S. Substantia nigra. In: Paxinos G, ed. The rat nervous system. New York: Academic Press, 1995;215–237.Google Scholar
  134. 134.
    Nestler EJ. Molecular mechanisms of drug addiction. Neuropharmacology 2004; 47 (Suppl 1):24–32.PubMedCrossRefGoogle Scholar
  135. 135.
    Gray JA, Joseph MH, Hemsley DR et al. The role of mesolimbic dopaminergic and retrohippocampal afferents to the nucleus accumbens in latent inhibition: implications for schizophrenia. Behav Brain Res 1995; 71(1–2):19–31.PubMedCrossRefGoogle Scholar
  136. 136.
    Pezze MA, Feldon J. Mesolimbic dopaminergic pathways in fear conditioning. Prog Neurobiol 2004; 74(5):301–320.PubMedCrossRefGoogle Scholar
  137. 137.
    Goldman S. Stem and progenitor cell-based therapy of the human central nervous system. Nat Biotechnol 2005; 23(7):862–871.PubMedCrossRefGoogle Scholar
  138. 138.
    Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature 2006; 441(7097):1094–1096.PubMedCrossRefGoogle Scholar
  139. 139.
    Lindvall O, Kokaia Z, Martinez-Serrano A. Stem cell therapy of human neurodegenerative disorders-how to make it work. Nat Med 2004; 10(Suppl):S42–50.PubMedCrossRefGoogle Scholar
  140. 140.
    Lindvall O, Bjorklund A. Cell therapy in Parkinson’s disease. NeuroRx 2004; 1(4):382–393.PubMedCrossRefGoogle Scholar
  141. 141.
    Winkler C, Kirik D, Bjorklund A. Cell transplantation in Parkinson’s disease: how can we make it work? Trends Neurosci 2005; 28(2):86–92.PubMedCrossRefGoogle Scholar
  142. 142.
    Saino-Saito S, Berlin R, Baker H. Dlx-1 and Dlx-2 expression in the adult mouse brain: relationship to dopaminergic phenotypic regulation. Journal of Comparative Neurology 2003; 461(1):18–30.PubMedCrossRefGoogle Scholar
  143. 143.
    Eisenstat DD, Liu JK, Mione M et al. DLX-1, DLX-2 and DLX-5 expression define distinct stages of basal forebrain differentiation. J Comp Neurol 1999; 414(2):217–237.PubMedCrossRefGoogle Scholar
  144. 144.
    Liu JK, Ghattas I, Liu S et al. Dlx genes encode DNA-binding proteins that are expressed in an overlapping and sequential pattern during basal ganglia differentiation. Dev Dyn 1997; 210(4):498–512.PubMedCrossRefGoogle Scholar
  145. 145.
    Bulfone A, Wang F, Hevner R et al. An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons. Neuron 1998; 21(6):1273–1282.PubMedCrossRefGoogle Scholar
  146. 146.
    Qiu M, Bulfone A, Martinez S et al. Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain. Genes Dev 1995; 9(20):2523–2538.PubMedCrossRefGoogle Scholar
  147. 147.
    Corbin JG, Gaiano N, Machold RP et al. The Gsh2 homeodomain gene controls multiple aspects of telencephalic development. Development 2000; 127(23):5007–5020.PubMedGoogle Scholar
  148. 148.
    Colombo E, Collombat P, Colasante G et al. Inactivation of Arx, the murine ortholog of the X-linked lissencephaly with ambiguous genitalia gene, leads to severe disorganization of the ventral telencephalon with impaired neuronal migration and differentiation. J Neurosci 2007; 27(17):4786–4798.PubMedCrossRefGoogle Scholar
  149. 149.
    Brown JP, Couillard-Despres S, Cooper-Kuhn CM et al. Transient expression of doublecortin during adult neurogenesis.J Comp Neurol 2003; 467(1):1–10.PubMedCrossRefGoogle Scholar
  150. 150.
    Gleeson JG, Lin PT, Flanagan LA et al. Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 1999; 23(2):257–271.PubMedCrossRefGoogle Scholar
  151. 151.
    Nacher J, Crespo C, McEwen BS. Doublecortin expression in the adult rat telencephalon. Eur J Neurosci 2001; 14(4):629–644.PubMedCrossRefGoogle Scholar
  152. 152.
    Ocbina PJ, Dizon ML, Shin L et al. Doublecortin is necessary for the migration of adult subventricular zone cells from neurospheres. Mol Cell Neurosci 2006; 33(2):126–135.PubMedCrossRefGoogle Scholar
  153. 153.
    Conover JC, Doetsch F, Garcia-Verdugo JM et al. Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Nat Neurosci 2000; 3(11):1091–1097.PubMedCrossRefGoogle Scholar
  154. 154.
    Holmberg J, Armulik A, Senti KA et al. Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis. Genes Dev 2005; 19(4):462–471.PubMedCrossRefGoogle Scholar
  155. 155.
    Guillemot F, Joyner AL. Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system. Mech Dev 1993; 42(3):171–185.PubMedCrossRefGoogle Scholar
  156. 156.
    Guillemot F, Lo LC, Johnson JE et al. Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons. Cell 1993; 75(3):463–476.PubMedCrossRefGoogle Scholar
  157. 157.
    Lo LC, Johnson JE, Wuenschell CW et al. Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural cresT-cells. Genes Dev 1991. 5(9):1524–1537.PubMedCrossRefGoogle Scholar
  158. 158.
    Parras CM, Galli R, Britz O et al. Mash1 specifies neurons and oligodendrocytes in the postnatal brain. EMBO J 2004; 23(22):4495–4505.PubMedCrossRefGoogle Scholar
  159. 159.
    Merson TD, Dixon MP, Collin C et al. The transcriptional coactivator Querkopf controls adult neurogenesis. J Neurosci 2006; 26(44):11359–11370.PubMedCrossRefGoogle Scholar
  160. 160.
    Givogri MI, de Planell M, Galbiati F et al. Notch signaling in astrocytes and neuroblasts of the adult subventricular zone in health and after cortical injury. Dev Neurosci 2006; 28(1–2):81–91.PubMedCrossRefGoogle Scholar
  161. 161.
    Higuchi M, Kiyama H, Hayakawa T et al. Differential expression of Notch1 and Notch2 in developing and adult mouse brain. Brain Res Mol Brain Res 1995; 29(2):263–272.PubMedCrossRefGoogle Scholar
  162. 162.
    Irvin DK, Nakano I, Paucar A et al. Patterns of Jagged1, Jagged2, Delta-like 1 and Delta-like 3 expression during late embryonic and postnatal brain development suggest miltiple functional roles in progenitors and differentiated cells. J Neurosci Res 2004; 75(3):330–343.PubMedCrossRefGoogle Scholar
  163. 163.
    Irvin DK, Zurcher SD, Nguyen T et al. Expression patterns of Notch1, Notch2 and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development. J Comp Neurol 2001; 436(2):167–181.PubMedCrossRefGoogle Scholar
  164. 164.
    Stump G, Durrer A, Klein AL et al. Notch1 and its ligands Delta-like and Jagged are expressed and active in distincT-cell populations in the postnatal mouse brain. Mech Dev 2002; 114(1–2):153–159.PubMedCrossRefGoogle Scholar
  165. 165.
    Hack MA, Sugimori M, Lundberg C et al. Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6. Mol Cell Neurosci 2004; 25(4):664–678.PubMedCrossRefGoogle Scholar
  166. 166.
    Ng KL, Li. JD, Cheng MY et al. Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling. Science 2005; 308(5730):1923–1927.PubMedCrossRefGoogle Scholar
  167. 167.
    Cremer H, Lange R, Christoph A et al. Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 1994; 367(6462):455–459.PubMedCrossRefGoogle Scholar
  168. 168.
    Ono K, Tomasiewicz H, Magnuson T et al. N-CAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid. Neuron 1994; 13(3):595–609.PubMedCrossRefGoogle Scholar
  169. 169.
    Tomasiewicz H, Ono K, Yee D et al. Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system.Neuron 1993; 11(6):1163–1174.PubMedCrossRefGoogle Scholar
  170. 170.
    Wichterle H, Garcia-Verdugo JM, Alvarez-Buylla A. Direct evidence for homotypic, glia-independent neuronal migration. Neuron 1997; 18(5):779–791.PubMedCrossRefGoogle Scholar
  171. 171.
    Hack I, Bancila M, Loulier K et al. Reelin is a detachment signal in tangential chain-migration during postnatal neurogenesis. Nat Neurosci 2002; 5(10):939–945.PubMedCrossRefGoogle Scholar
  172. 172.
    Balordi F, Fishell G. Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons. J Neurosci 2007; 27(22):5936–5947.PubMedCrossRefGoogle Scholar
  173. 173.
    Machold R, Hayashi S, Rutlin M et al. Sonic hedgehog is required for progenitor cell maintenance in telencephatic stem cell niches. Neuron 2003; 39(6):937–950.PubMedCrossRefGoogle Scholar
  174. 174.
    Palma V, Lim DA, Dahmane N et al. Sonic hedgehod controls stem cell behavior in the postnatal and adult brain. Development 2005; 132(2):335–344.PubMedCrossRefGoogle Scholar
  175. 175.
    Hu H. Chemorepulsion of neuronal migration by Slit2 in the develiping mammalian forebrain. Neuron 1999; 23(4):703–711.PubMedCrossRefGoogle Scholar
  176. 176.
    Li HS, Chen JH, Wu W et al. Vertebrate slit, a secreted ligand for the transmembrane protein round-about, is a repellent for olfactory bulb axons. Cell 1999; 96(6):807–818.PubMedCrossRefGoogle Scholar
  177. 177.
    Marillat V, Cases O, Nguyen-Ba-Charvet KT et al. Spatiotemporal expression patterns of slit and robo genes in the rat brain. J Comp Neurol 2002; 442(2):130–155.PubMedCrossRefGoogle Scholar
  178. 178.
    Wu W, Wong K, Chen J et al. Directional guidance of neuronal migration in the olfactory system by the protein Slit. Nature 1999; 400(6742):331–336.PubMedCrossRefGoogle Scholar
  179. 179.
    Chen JH, Wen L, Dupuis S et al. The N-terminal leucine-rich regions in Slit are sufficient to repel olfactory bulb axons and subventricular zone neurons. J Neurosci 2001; 21(5):1548–1556.PubMedGoogle Scholar
  180. 180.
    Sawamoto K, Wichterle H, Gonzalez-Perez O et al. New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 2006; 311(5761):629–632.PubMedCrossRefGoogle Scholar
  181. 181.
    Saghatelyan A, de Chevigny A, Schachner M et al. Tenascin-R mediates activity-dependent recruitment of neuroblasts in the adult mouse forebrain. Nat Neurosci 2004; 7(4):347–356.PubMedCrossRefGoogle Scholar
  182. 182.
    Hallonet M, Hollemann T, Wehr R et al. Vax1 is a novel homeobox-containing gene expressed in the developing anterior ventral forebrain. Development 1998; 125(14):2599–2610.PubMedGoogle Scholar
  183. 183.
    Soria JM, Taglialatela P, Gil-Perotin S et al. Defective postnatal neurogenesis and disorganization of the rostral migratory stream in absence of the Vax1 homeobox gene. J Neurosci 2004; 24(49):11171–11181.PubMedCrossRefGoogle Scholar
  184. 184.
    Levy NS, Bakalyar HA, Reed RR. Signal transduction in olfactory neurons. J Steroid Biochem Mol Biol 1991; 39(4B):633–637.PubMedCrossRefGoogle Scholar
  185. 185.
    Long JE, Garel S, Alvarez-Dolado M et al. Dlx-dependent and independent regulation of olfactory bulb interneuron differentiation. J Neurosci 2007; 27(12):3230–3243.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Department of Neurology and Neuroscience, Weill Cornell Medical CollegeBurke Medical Research InstituteWhite PlainsUSA

Personalised recommendations