Home LiteratureArticle Details
PMID: 10436056 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Excess of serotonin (5-HT) alters the segregation of ispilateral and contralateral retinal projections in monoamine oxidase A knock-out mice: possible role of 5-HT uptake in retinal ganglion cells during development.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 19 ·No. 16 ·1999-08-15 ·Pages 7007-24

Upton AL, Salichon N, Lebrand C, Ravary A, Blakely R, Seif I, Gaspar P

Abstract

Retinal ganglion cell (RGCs) project to the ipsilateral and contralateral sides of the brain in the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). Projections from both eyes are initially intermingled until postnatal day 3 (P3) but segregate into eye-specific layers by P8. We report that this segregation does not occur in monoamine oxidase A knock-out mice (MAOA-KO) that have elevated brain levels of serotonin (5-HT) and noradrenaline. The abnormal development of retinal projections can be reversed by inhibiting 5-HT synthesis from P0 to P15. We found that in MAOA-KO mice, 5-HT accumulates in a subpopulation of RGCs and axons during embryonic and early postnatal development. The RGCs do not synthesize 5-HT but reuptake the amine from the extracellular space. In both MAOA-KO and normal mice, high-affinity uptake of 5-HT and serotonin transporter (SERT) immunoreactivity are observed in retinal axons from the optic cup to retinal terminal fields in the SC and dLGN. In the dLGN, transient SERT labeling corresponds predominantly to the ipsilateral retinal projection fields. We show that, in addition to SERT, developing RGCs also transiently express the vesicular monoamine transporter gene VMAT2: thus, retinal axons could store 5-HT in synaptic vesicles and possibly use it as a borrowed neurotransmitter. Finally we show that the 5-HT-1B receptor gene is expressed by RGCs throughout the retina from E15 until adult life. Activation of this receptor is known, from previous studies, to reduce retinotectal activity; thus 5-HT in excess could inhibit activity-dependent segregation mechanisms. A hypothesis is proposed whereby, during normal development, localized SERT expression could confer specific neurotransmission properties on a subset of RGCs and could be important in the fine-tuning of retinal projections.

MeSH Terms
Animals Carrier Proteins/physiology Functional Laterality/physiology Geniculate Bodies/metabolism Membrane Glycoproteins/physiology Membrane Transport Proteins Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Monoamine Oxidase/genetics Nerve Tissue Proteins/physiology Norepinephrine/metabolism Retina/physiology Retinal Ganglion Cells/physiology Serotonin/metabolism,physiology Serotonin Plasma Membrane Transport Proteins Superior Colliculi/metabolism Visual Pathways/physiology
Chemicals
Carrier Proteins Membrane Glycoproteins Membrane Transport Proteins Nerve Tissue Proteins Serotonin Plasma Membrane Transport Proteins Slc6a4 protein, mouse Serotonin Monoamine Oxidase Norepinephrine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Upton A L
Institut National de la Santé et de la Recherche Médicale U106, Hôpital de la Salpêtrière, 75651 Paris cedex 13, France.
Salichon N
Lebrand C
Ravary A
Blakely R
Seif I
Gaspar P
References (75)
75 references, click to expand
  1. Quantitative evaluation of 5-hydroxytryptamine (serotonin) neuronal release and uptake: an investigation of extrasynaptic transmission.
    J Neurosci. 1998 Jul 1;18(13):4854-60 PMID: 9634551
  2. Stages of growth of hamster retinofugal axons: implications for developing axonal pathways with multiple targets.
    J Neurosci. 1991 Feb;11(2):485-504 PMID: 1992013
  3. Expression of 5-HT7 receptor mRNA in rat brain during postnatal development.
    Neurosci Lett. 1997 May 9;227(1):53-6 PMID: 9178857
  4. Effects of monoamine oxidase A inhibition on barrel formation in the mouse somatosensory cortex: determination of a sensitive developmental period.
    J Comp Neurol. 1998 Apr 6;393(2):169-84 PMID: 9548695
  5. Neurogenesis in the retinal ganglion cell layer of the rat.
    Neuroscience. 1992;46(2):419-29 PMID: 1542415
  6. Subcellular localization of 5-HT1B binding sites in the stratum griseum superficiale of the rat superior colliculus: An electron microscopic quantitative autoradiographic study.
    Synapse. 1996 Nov;24(3):203-12 PMID: 8923659
  7. Activity and the control of ganglion cell death in the rat retina.
    Proc Natl Acad Sci U S A. 1984 Sep;81(17):5589-93 PMID: 6591206
  8. Plasma membrane transporters of serotonin, dopamine, and norepinephrine mediate serotonin accumulation in atypical locations in the developing brain of monoamine oxidase A knock-outs.
    J Neurosci. 1998 Sep 1;18(17):6914-27 PMID: 9712661
  9. Development of the rat's uncrossed retinotectal pathway and its relation to plasticity studies.
    Science. 1979 Aug 17;205(4407):698-700 PMID: 462177
  10. Serotonin promotes the survival of cortical glutamatergic neurons in vitro.
    Exp Neurol. 1997 Nov;148(1):205-14 PMID: 9398462
  11. Impulse activity and the patterning of connections during CNS development.
    Neuron. 1990 Dec;5(6):745-56 PMID: 2148486
  12. Postnatal development of retinal projections to the lateral geniculate body in Syrian hamsters.
    Brain Res. 1978 Feb 24;142(2):343-52 PMID: 630390
  13. Retinal ganglion cell death and terminal field retraction in the developing rodent visual system.
    Brain Res. 1984 Mar;315(1):81-96 PMID: 6326969
  14. Glutamate-like immunoreactivity in retinal terminals of the mouse suprachiasmatic nucleus.
    Eur J Neurosci. 1993 Apr 1;5(4):368-81 PMID: 7903187
  15. Origins of crossed and uncrossed retinal projections in pigmented and albino mice.
    J Comp Neurol. 1980 Jun;191(3):383-412 PMID: 7410600
  16. Genetic and environmental control of variation in retinal ganglion cell number in mice.
    J Neurosci. 1996 Nov 15;16(22):7193-205 PMID: 8929428
  17. Prenatal development of the serotonin transporter in mouse brain.
    Cell Tissue Res. 1997 Aug;289(2):211-21 PMID: 9211824
  18. Development of topographic order in the mammalian retinocollicular projection.
    J Neurosci. 1992 Apr;12(4):1212-32 PMID: 1313491
  19. Competition in retinogeniculate patterning driven by spontaneous activity.
    Science. 1998 Mar 27;279(5359):2108-12 PMID: 9516112
  20. Effects of intraocular tetrodotoxin on the development of the retinocollicular pathway in the Syrian hamster.
    J Comp Neurol. 1989 Apr 15;282(3):371-88 PMID: 2715388
  21. Prenatal expression of 5-HT1C and 5-HT2 receptors in the rat central nervous system.
    Exp Neurol. 1993 Apr;120(2):186-201 PMID: 8491279
  22. Maturational gradients in the retina of the ferret.
    J Comp Neurol. 1996 Nov 11;375(2):252-73 PMID: 8915829
  23. Postnatal changes in arborization patterns of murine retinocollicular axons.
    J Comp Neurol. 1986 Apr 15;246(3):395-408 PMID: 3700722
  24. Exogenous monoamines affect the segregation of retinogeniculate fibers in developing rats.
    Brain Res. 1985 Sep;354(1):135-40 PMID: 3930005
  25. Ganglion cell death during development of ipsilateral retino-collicular projection in golden hamster.
    Nature. 1984 Mar 22-28;308(5957):362-5 PMID: 6709042
  26. Identification and characterization of antidepressant-sensitive serotonin transporter proteins using site-specific antibodies.
    J Neurosci. 1995 Feb;15(2):1261-74 PMID: 7869097
  27. A study in developing visual systems with a new method of staining neurones and their processes in fixed tissue.
    Development. 1987 Dec;101(4):697-713 PMID: 2460302
  28. Serotonergic innervation of the lateral geniculate nucleus of the rat during postnatal development: a light and electron microscopic immunocytochemical analysis.
    J Comp Neurol. 1995 Dec 25;363(4):532-544 PMID: 8847416
  29. Genetic control of retinal ganglion cell projections.
    J Comp Neurol. 1978 Dec 1;182(3):399-421 PMID: 102659
  30. Topographic guidance labels in a sensory projection to the forebrain.
    Neuron. 1998 Dec;21(6):1303-13 PMID: 9883724
  31. Transient developmental expression of monoamine transporters in the rodent forebrain.
    J Comp Neurol. 1998 Nov 30;401(4):506-24 PMID: 9826275
  32. Postnatal changes in the uncrossed retinal projection of pigmented and albino Syrian hamsters and the effects of monocular enucleation.
    J Comp Neurol. 1995 Jun 26;357(2):181-203 PMID: 7545188
  33. p-Chlorophenylalanine: a specific depletor of brain serotonin.
    J Pharmacol Exp Ther. 1966 Dec;154(3):499-516 PMID: 5297133
  34. Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA.
    Science. 1995 Jun 23;268(5218):1763-6 PMID: 7792602
  35. Birth dates of retinal ganglion cells giving rise to the crossed and uncrossed optic projections in the mouse.
    Proc R Soc Lond B Biol Sci. 1985 Mar 22;224(1234):57-77 PMID: 2581263
  36. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors.
    Brain Res. 1985 Nov 4;346(2):231-49 PMID: 4052777
  37. Modulation of retinotectal transmission by presynaptic 5-HT1B receptors in the superior colliculus of the adult hamster.
    J Neurophysiol. 1994 Jul;72(1):3-13 PMID: 7965014
  38. Effect of serotonin depletion on vibrissa-related patterns of thalamic afferents in the rat's somatosensory cortex.
    J Neurosci. 1994 Dec;14(12):7594-607 PMID: 7996198
  39. Reduction in the percentage of serotoninergic axons making synapses during the development of the superficial layers of the hamster's superior colliculus.
    Brain Res Dev Brain Res. 1993 Sep 17;75(1):131-5 PMID: 8222208
  40. Neurotransmitters as growth regulatory signals: role of receptors and second messengers.
    Trends Neurosci. 1993 Jun;16(6):233-40 PMID: 7688165
  41. Cloning and expression of a functional serotonin transporter from rat brain.
    Nature. 1991 Nov 7;354(6348):66-70 PMID: 1944572
  42. Quantitative immunogold evidence for enrichment of glutamate but not aspartate in synaptic terminals of retino-geniculate, geniculo-cortical, and cortico-geniculate axons in the cat.
    Vis Neurosci. 1994 Jul-Aug;11(4):675-81 PMID: 7918218
  43. Increased serotoninergic innervation of the hamster's superior colliculus alters retinotectal projections.
    J Comp Neurol. 1993 Aug 15;334(3):397-409 PMID: 8376625
  44. Serotonin receptor activation enhances neurite outgrowth of thalamic neurones in rodents.
    Neurosci Lett. 1999 Jul 9;269(2):87-90 PMID: 10430511
  45. Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map.
    Cell. 1995 Aug 11;82(3):371-81 PMID: 7634327
  46. Monoaminergic afferents to cortex modulate structural plasticity in the barrelfield of the mouse.
    Brain Res Dev Brain Res. 1994 Feb 18;77(2):189-202 PMID: 8174228
  47. Projection lines and the ipsilateral retino-geniculate pathway in the hooded rat.
    Neuroscience. 1983 Dec;10(4):1233-47 PMID: 6664492
  48. Lack of barrels in the somatosensory cortex of monoamine oxidase A-deficient mice: role of a serotonin excess during the critical period.
    Neuron. 1996 Feb;16(2):297-307 PMID: 8789945
  49. Retinal axon divergence in the optic chiasm: dynamics of growth cone behavior at the midline.
    J Neurosci. 1994 Nov;14(11 Pt 2):7024-39 PMID: 7965096
  50. Synaptic activity and the construction of cortical circuits.
    Science. 1996 Nov 15;274(5290):1133-8 PMID: 8895456
  51. Prenatal and postnatal development of retinogeniculate and retinocollicular projections in the mouse.
    J Comp Neurol. 1984 Dec 20;230(4):552-75 PMID: 6520251
  52. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases.
    Cell. 1995 Aug 11;82(3):359-70 PMID: 7634326
  53. A study of the retinal ganglion cell which has an uncrossed bifurcating axon in the albino rat.
    Brain Res. 1989 May 29;488(1-2):143-8 PMID: 2743111
  54. Effects of 5-HT on thalamocortical synaptic transmission in the developing rat.
    J Neurophysiol. 1994 Nov;72(5):2438-50 PMID: 7884470
  55. Molecular cloning and characterization of a rat brain cDNA encoding a 5-hydroxytryptamine1B receptor.
    EMBO J. 1991 Dec;10(13):4017-23 PMID: 1836757
  56. Development of the mammalian retinogeniculate pathway: target finding, transient synapses and binocular segregation.
    J Exp Biol. 1990 Oct;153:85-104 PMID: 2280230
  57. Disruption of retinogeniculate afferent segregation by antagonists to NMDA receptors.
    Nature. 1991 Jun 13;351(6327):568-70 PMID: 1675433
  58. Serotonin 1B receptors in the developing somatosensory and visual cortices are located on thalamocortical axons.
    Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):153-7 PMID: 8419917
  59. A comparison of pattern formation by thalamocortical and serotonergic afferents in the rat barrel field cortex.
    Cereb Cortex. 1991 Sep-Oct;1(5):380-9 PMID: 1822748
  60. [Physiological and anatomical study of the retinogeniculate projections in the mouse].
    C R Seances Acad Sci III. 1983 Jan 24;296(3):157-62 PMID: 6404518
  61. Development of the crossed retinocollicular projection in the mouse.
    J Comp Neurol. 1986 Jun 15;248(3):410-21 PMID: 3722464
  62. Effects of serotonin on retinotectal-, corticotectal-, and glutamate-induced activity in the superior colliculus of the hamster.
    J Neurophysiol. 1993 Aug;70(2):723-32 PMID: 8105037
  63. Expression and regulation of the bovine vesicular monoamine transporter gene.
    FEBS Lett. 1993 Nov 29;335(1):27-32 PMID: 7902299
  64. An immunohistochemical study of serotonin neuron development in the rat: ascending pathways and terminal fields.
    Brain Res Bull. 1982 Apr;8(4):389-430 PMID: 6178481
  65. Prenatal tetrodotoxin infusion blocks segregation of retinogeniculate afferents.
    Science. 1988 Oct 7;242(4875):87-9 PMID: 3175636
  66. The early development of retinal ganglion cells with uncrossed axons in the mouse: retinal position and axonal course.
    Development. 1990 Mar;108(3):515-23 PMID: 2340812
  67. Pharmacological characterization of serotonin synthesis and uptake suggest a false transmitter role for serotonin in the pituitary intermediate lobe.
    Neurosci Res. 1994 Dec;21(2):143-9 PMID: 7724065
  68. Thalamic relay of spontaneous retinal activity prior to vision.
    Neuron. 1996 Nov;17(5):863-74 PMID: 8938119
  69. Augmentation of serotonin in the developing superior colliculus alters the normal development of the uncrossed retinotectal projection.
    J Comp Neurol. 1998 Mar 30;393(1):84-92 PMID: 9520103
  70. Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina.
    Science. 1991 May 17;252(5008):939-43 PMID: 2035024
  71. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).
    Pharmacol Rev. 1994 Jun;46(2):157-203 PMID: 7938165
  72. Spontaneous impulse activity of rat retinal ganglion cells in prenatal life.
    Science. 1988 Oct 7;242(4875):90-1 PMID: 3175637
  73. Novel effects of serotonin on neurite outgrowth in neurons cultured from embryos of Helisoma trivolvis.
    J Neurobiol. 1991 Mar;22(2):182-94 PMID: 2030341
  74. RETINAL DEGENERATION IN THE MOUSE: LOCATION OF THE RD LOCUS IN LINKAGE GROUP XVII.
    J Hered. 1965 Jan-Feb;56:23-9 PMID: 14276177
  75. Transient uptake and storage of serotonin in developing thalamic neurons.
    Neuron. 1996 Nov;17(5):823-35 PMID: 8938116
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
1999-08-15
Pages
7007-24
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6782873
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2