Home LiteratureArticle Details
PMID: 17940915 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Requirement of TrkB for synapse elimination in developing cerebellar Purkinje cells.

Brain cell biology ·Vol. 35 ·No. 1 ·2006-02-00 ·Pages 87-101

Bosman LW, Hartmann J, Barski JJ, Lepier A, Noll-Hussong M, Reichardt LF, Konnerth A

Abstract

The receptor tyrosine kinase TrkB and its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), are critically important for growth, survival and activity-dependent synaptic strengthening in the central nervous system. These TrkB-mediated actions occur in a highly cell-type specific manner. Here we report that cerebellar Purkinje cells, which are richly endowed with TrkB receptors, develop a normal morphology in trkB-deficient mice. Thus, in contrast to other types of neurons, Purkinje cells do not need TrkB for dendritic growth and spine formation. Instead, we find a moderate delay in the maturation of GABAergic synapses and, more importantly, an abnormal multiple climbing fiber innervation in Purkinje cells in trkB-deficient mice. Thus, our results demonstrate an involvement of TrkB receptors in synapse elimination and reveal a new role for receptor tyrosine kinases in the brain.

MeSH Terms
Animals Brain-Derived Neurotrophic Factor/metabolism Cell Shape/physiology Dendrites/physiology,ultrastructure Dendritic Spines/physiology Inhibitory Postsynaptic Potentials/physiology Mice Mice, Inbred BALB C Mice, Inbred ICR Mice, Mutant Strains Purkinje Cells/cytology,physiology,ultrastructure Receptor, trkB/genetics,metabolism Synapses/physiology gamma-Aminobutyric Acid/physiology
Chemicals
Brain-Derived Neurotrophic Factor gamma-Aminobutyric Acid Receptor, trkB
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bosman Laurens W J
Institut für Neurowissenschaften, Technische Universität München, Biedersteiner Strasse 29, 80802, München, Germany.
Hartmann Jana
Barski Jaroslaw J
Lepier Alexandra
Noll-Hussong Michael
Reichardt Louis F
Konnerth Arthur
References (60)
60 references, click to expand
  1. The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum.
    J Neurosci. 1992 Mar;12(3):1063-76 PMID: 1312132
  2. Transgenic brain-derived neurotrophic factor modulates a developing cerebellar inhibitory synapse.
    Learn Mem. 1999 May-Jun;6(3):276-83 PMID: 10492009
  3. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system.
    Genes Dev. 2000 Dec 1;14(23):2919-37 PMID: 11114882
  4. An autoradiographic analysis of histogenesis in the mouse cerebellum.
    Exp Neurol. 1961 Oct;4:277-96 PMID: 14473282
  5. Dendritic organization in the neurons of the visual and motor cortices of the cat.
    J Anat. 1953 Oct;87(4):387-406 PMID: 13117757
  6. Structural characterization of marginal (lamina I) spinal cord neurons in the cat: a Golgi study.
    J Comp Neurol. 1999 Nov 22;414(3):315-33 PMID: 10516599
  7. The histogenesis of the mouse cerebellum as studied by its tritiated thymidine uptake.
    J Comp Neurol. 1960 Apr;114:137-59 PMID: 13840582
  8. Suppression of LTD in cultured Purkinje cells deficient in the glutamate receptor delta 2 subunit.
    Neuroreport. 1995 Feb 15;6(3):524-6 PMID: 7766857
  9. TrkB signaling modulates spine density and morphology independent of dendrite structure in cultured neonatal Purkinje cells.
    J Neurosci. 1998 Nov 1;18(21):8559-70 PMID: 9786964
  10. TrkB and TrkC signaling are required for maturation and synaptogenesis of hippocampal connections.
    J Neurosci. 1998 Sep 15;18(18):7336-50 PMID: 9736654
  11. TrkB receptor signaling is required for establishment of GABAergic synapses in the cerebellum.
    Nat Neurosci. 2002 Mar;5(3):225-33 PMID: 11836532
  12. Spatially resolved calcium dynamics of mammalian Purkinje cells in cerebellar slice.
    Science. 1988 Nov 4;242(4879):773-7 PMID: 2847315
  13. Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure.
    J Neurosci. 2002 Feb 15;22(4):1316-27 PMID: 11850459
  14. Inhibition of ocular dominance column formation by infusion of NT-4/5 or BDNF.
    Science. 1995 Mar 17;267(5204):1662-6 PMID: 7886458
  15. TrkB has a cell-autonomous role in the establishment of hippocampal Schaffer collateral synapses.
    J Neurosci. 2005 Apr 13;25(15):3774-86 PMID: 15829629
  16. Immunocytochemical localization of TrkB in the central nervous system of the adult rat.
    J Comp Neurol. 1997 Feb 3;378(1):135-57 PMID: 9120052
  17. Neurotrophins and neuronal differentiation in the central nervous system.
    Cell Mol Life Sci. 2001 Jul;58(8):1054-60 PMID: 11529498
  18. Role of neurotrophin receptor TrkB in the maturation of rod photoreceptors and establishment of synaptic transmission to the inner retina.
    J Neurosci. 1999 Oct 15;19(20):8919-30 PMID: 10516311
  19. The Ca-calmodulin-dependent protein kinase cascade.
    Trends Biochem Sci. 1999 Jun;24(6):232-6 PMID: 10366852
  20. Postsynaptic TrkB signaling has distinct roles in spine maintenance in adult visual cortex and hippocampus.
    Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1071-6 PMID: 16418274
  21. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons.
    Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11412-7 PMID: 9736750
  22. Purkinje cell dendritic tree development in the absence of excitatory neurotransmission and of brain-derived neurotrophic factor in organotypic slice cultures.
    Neuroscience. 2004;127(1):137-45 PMID: 15219676
  23. Neonatal development of the rat visual cortex: synaptic function of GABAA receptor alpha subunits.
    J Physiol. 2002 Nov 15;545(1):169-81 PMID: 12433958
  24. Functional differentiation of multiple climbing fiber inputs during synapse elimination in the developing cerebellum.
    Neuron. 2003 Jun 5;38(5):785-96 PMID: 12797962
  25. Synaptic- and agonist-induced excitatory currents of Purkinje cells in rat cerebellar slices.
    J Physiol. 1991 Mar;434:183-213 PMID: 1673717
  26. Cerebellar defects in Ca2+/calmodulin kinase IV-deficient mice.
    J Neurosci. 2000 Nov 15;20(22):RC107 PMID: 11069976
  27. A two-photon and second-harmonic microscope.
    Methods. 2003 May;30(1):3-15 PMID: 12695099
  28. Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development.
    J Neurosci. 2001 Dec 15;21(24):9701-12 PMID: 11739579
  29. Tree asymmetry--a sensitive and practical measure for binary topological trees.
    Bull Math Biol. 1992 Sep;54(5):759-84 PMID: 1638259
  30. Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice.
    Cell. 1994 Oct 21;79(2):377-88 PMID: 7954803
  31. Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death.
    Cell. 1993 Oct 8;75(1):113-22 PMID: 8402890
  32. Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galphaq.
    Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14089-94 PMID: 9391157
  33. Trk receptors: roles in neuronal signal transduction.
    Annu Rev Biochem. 2003;72:609-42 PMID: 12676795
  34. Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons.
    Nat Neurosci. 2005 Feb;8(2):164-72 PMID: 15665879
  35. Early climbing fiber interactions with Purkinje cells in the postnatal mouse cerebellum.
    J Comp Neurol. 1990 Jul 1;297(1):77-90 PMID: 1695909
  36. Truncated and full-length TrkB receptors regulate distinct modes of dendritic growth.
    Nat Neurosci. 2000 Apr;3(4):342-9 PMID: 10725923
  37. Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1.
    Neuron. 1997 Jan;18(1):71-9 PMID: 9010206
  38. Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells.
    J Neurosci. 1995 Jul;15(7 Pt 1):4970-81 PMID: 7623126
  39. TrkB receptor ligands promote activity-dependent inhibitory synaptogenesis.
    J Neurosci. 2000 Jul 15;20(14):5367-73 PMID: 10884321
  40. Signal transduction mediated by the truncated trkB receptor isoforms, trkB.T1 and trkB.T2.
    J Neurosci. 1997 Apr 15;17(8):2683-90 PMID: 9092589
  41. Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluR delta 2 mutant mice.
    Cell. 1995 Apr 21;81(2):245-52 PMID: 7736576
  42. Synapses on the Purkinje cell spines in the mouse. An electronmicroscopic study.
    Brain Res. 1967 May;5(1):15-30 PMID: 6035937
  43. Transient expression of GABAA receptor alpha2 and alpha3 subunits in differentiating cerebellar neurons.
    Brain Res Dev Brain Res. 2004 Feb 20;148(2):169-77 PMID: 14766194
  44. Genesis of dendritic spines: insights from ultrastructural and imaging studies.
    Nat Rev Neurosci. 2004 Jan;5(1):24-34 PMID: 14708001
  45. Phospholipase cbeta4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum.
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15724-9 PMID: 9861037
  46. Synaptic currents in cerebellar Purkinje cells.
    Proc Natl Acad Sci U S A. 1990 Apr;87(7):2662-5 PMID: 1969639
  47. trkB, a neural receptor protein-tyrosine kinase: evidence for a full-length and two truncated receptors.
    Mol Cell Biol. 1991 Jan;11(1):143-53 PMID: 1846020
  48. Postnatal development of the cerebellar cortex in the rat. II. Phases in the maturation of Purkinje cells and of the molecular layer.
    J Comp Neurol. 1972 Aug;145(4):399-463 PMID: 5044254
  49. Eradication of cerebellar granular cells alters the developmental expression of trk receptors in the rat inferior olive.
    Int J Dev Neurosci. 1998 Feb;16(1):49-62 PMID: 9664222
  50. TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons.
    Genes Dev. 1996 Nov 15;10(22):2849-58 PMID: 8918886
  51. Impaired synapse elimination during cerebellar development in PKC gamma mutant mice.
    Cell. 1995 Dec 29;83(7):1223-31 PMID: 8548808
  52. CREB: a major mediator of neuronal neurotrophin responses.
    Neuron. 1997 Nov;19(5):1031-47 PMID: 9390517
  53. Fate of the multiple innervation of cerebellar Purkinje cells by climbing fibers in immature control, x-irradiated and hypothyroid rats.
    Brain Res. 1981 Jan;227(1):59-71 PMID: 7470934
  54. Neurotrophins: roles in neuronal development and function.
    Annu Rev Neurosci. 2001;24:677-736 PMID: 11520916
  55. Distinct roles of Galpha(q) and Galpha11 for Purkinje cell signaling and motor behavior.
    J Neurosci. 2004 Jun 2;24(22):5119-30 PMID: 15175381
  56. Mapping calcium transients in the dendrites of Purkinje cells from the guinea-pig cerebellum in vitro.
    J Physiol. 1987 Aug;389:319-36 PMID: 3681730
  57. Ethanol exposure alters neurotrophin receptor expression in the rat central nervous system: Effects of prenatal exposure.
    J Neurobiol. 2004 Jul;60(1):101-13 PMID: 15188276
  58. Abnormal cerebellar development and foliation in BDNF-/- mice reveals a role for neurotrophins in CNS patterning.
    Neuron. 1997 Aug;19(2):269-81 PMID: 9292718
  59. Mechanism of TrkB-mediated hippocampal long-term potentiation.
    Neuron. 2002 Sep 26;36(1):121-37 PMID: 12367511
  60. Regulation of dendritic growth by calcium and neurotrophin signaling.
    Prog Brain Res. 2005;147:17-27 PMID: 15581694
Article Info
Journal
Brain cell biology
Abbr.
Brain Cell Biol
ISSN
1559-7105
DOI
10.1007/s11068-006-9002-z
Published
2006-02-00
Epub
2007-00-01
Pages
87-101
Language
English
Region
United States
NLM ID
101272887
PMCID
PMC3303929
Subset
IM
Grants
NINDS NIH HHS · P01 NS016033 · United States
NINDS NIH HHS · P01 NS016033-250014 · United States
External Links
PubMed source DOI: 10.1007/s11068-006-9002-z PMC Full Text
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