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Deletion of the GluRδ2 Receptor in the Hotfoot Mouse Mutant Causes Granule Cell Loss, Delayed Purkinje Cell Death, and Reductions in Purkinje Cell Dendritic Tree Area

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Abstract

Recent studies have found that in the cerebellum, the δ2 glutamate receptor (GluRδ2) plays a key role in regulating the differentiation of parallel fiber-Purkinje synapses and mediating key physiological functions in the granule cell-Purkinje cell circuit. In the hotfoot mutant or GluRδ2 knockout mice, the absence of GluRδ2 expression results in impaired motor-related tasks, ataxia, and disruption of long-term depression at parallel fiber-Purkinje cell synapses. The goal of this study was to determine the long-term consequences of deletion of GluRδ2 expression in the hotfoot mutant (GluRδ2ho/ho) on Purkinje and granule cell survival and Purkinje cell dendritic differentiation. Quantitative estimates of Purkinje and granule cell numbers in 3-, 12-, and 20-month-old hotfoot mutants and wild-type controls showed that Purkinje cell numbers are within control values at 3 and 12 months in the hotfoot mutant but reduced by 20 % at 20 months compared with controls. In contrast, the number of granule cells is significantly reduced from 3 months onwards in GluRδ2ho/ho mutant mice compared to wild-type controls. Although the overall structure of Purkinje cell dendrites does not appear to be altered, there is a significant 27 % reduction in the cross-sectional area of Purkinje cell dendritic trees in the 20-month-old GluRδ2ho/ho mutants. The interpretation of the results is that the GluRδ2 receptor plays an important role in the long-term organization of the granule-Purkinje cell circuit through its involvement in the regulation of parallel fiber-Purkinje cell synaptogenesis and in the normal functioning of this critical cerebellar circuit.

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References

  1. Yuzaki M. The delta2 glutamate receptor: 10 years later. Neurosci Res. 2003;46(1):11–22.

    Article  CAS  PubMed  Google Scholar 

  2. Vogel MW, Caston J, Yuzaki M, Mariani J. The Lurcher mouse: fresh insights from an old mutant. Brain Res. 2007;1140:4–18.

    Article  CAS  PubMed  Google Scholar 

  3. Yuzaki M. The delta2 glutamate receptor: a key molecule controlling synaptic plasticity and structure in Purkinje cells. Cerebellum. 2004;3(2):89–93.

    Article  CAS  PubMed  Google Scholar 

  4. Lomeli H, Sprengel R, Lauris DJ, Kohr G, Herb A, Seeburg PH, et al. The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family. FEBS Lett. 1993;315:318–22.

    Article  CAS  PubMed  Google Scholar 

  5. Araki K, Meguro H, Kushiya E, Takayama C, Inoue Y, Mishina M. Selective expression of the glutamate receptor channel d2 subunit in cerebellar Purkinje cells. Biochem Biophys Res Comm. 1993;197:1267–76.

    Article  CAS  PubMed  Google Scholar 

  6. Kohda K, Kakegawa W, Yuzaki M. Unlocking the secrets of the d2 glutamate receptor. Commun Integr Biol. 2013;66:e26466.

    Article  Google Scholar 

  7. Kashiwabuchi N, Ikeda K, Araki K, Hirano T, Shibuki K, Takayama C, et al. Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluR delta 2 mutant mice. Cell. 1995;81:245–52.

    Article  CAS  PubMed  Google Scholar 

  8. Hashimoto K, Ichikawa R, Takechi H, Inoue Y, Aiba A, Sakimura K, et al. 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;21(24):9701–12.

    CAS  PubMed  Google Scholar 

  9. Kato AS, Knierman MD, Siuda ER, Isaac JT, Nisenbaum ES, Bredt DS. Glutamate receptor delta2 associates with metabotropic glutamate receptor 1 (mGluR1), protein kinase Cgamma, and canonical transient receptor potential 3 and regulates mGluR1-mediated synaptic transmission in cerebellar Purkinje neurons. J Neurosci. 2012;32(44):15296–308.

    Article  CAS  PubMed  Google Scholar 

  10. Kakegawa W, Kohda K, Yuzaki M. The {delta}2 “ionotropic” glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity. J Physiol. 2007;16:16.

    Google Scholar 

  11. Kakegawa W, Miyoshi Y, Hamase K, Matsuda S, Matsuda K, Kohda K, et al. D-serine regulates cerebellar LTD and motor coordination through the delta2 glutamate receptor. Nat Neurosci. 2011;14(5):603–11.

    Article  CAS  PubMed  Google Scholar 

  12. Naur P, Hansen KB, Kristensen AS, Dravid SM, Pickering DS, Olsen L, et al. Ionotropic glutamate-like receptor delta2 binds D-serine and glycine. Proc Natl Acad Sci U S A. 2007;104(35):14116–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ady V, Perroy J, Tricoire L, Piochon C, Dadak S, Chen X, et al. Type 1 metabotropic glutamate receptors (mGlu1) trigger the gating of GluD2 delta glutamate receptors. EMBO Rep. 2014;15(1):103–9.

    Article  CAS  PubMed  Google Scholar 

  14. Ito-Ishida A, Miyazaki T, Miura E, Matsuda K, Watanabe M, Yuzaki M, et al. Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation. Neuron. 2012;76(3):549–64.

    Article  CAS  PubMed  Google Scholar 

  15. Matsuda K, Yuzaki M. Cbln1 and the delta2 glutamate receptor—an orphan ligand and an orphan receptor find their partners. Cerebellum. 2012;11(1):78–84.

    Article  CAS  PubMed  Google Scholar 

  16. Yuzaki M. Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers. Eur J Neurosci. 2010;32(2):191–7.

    Article  PubMed  Google Scholar 

  17. Matsuda K, Miura E, Miyazaki T, Kakegawa W, Emi K, Narumi S, et al. Cbln1 is a ligand for an orphan glutamate receptor delta2, a bidirectional synapse organizer. Science. 2010;328(5976):363–8.

    Article  CAS  PubMed  Google Scholar 

  18. Matsuda K, Yuzaki M. Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. Eur J Neurosci. 2011;33(8):1447–61.

    Article  PubMed  Google Scholar 

  19. Yuzaki M. Cbln1 and its family proteins in synapse formation and maintenance. Curr Opin Neurobiol. 2011;21(2):215–20.

    Article  CAS  PubMed  Google Scholar 

  20. Kohda K, Kakegawa W, Matsuda S, Yamamoto T, Hirano H, Yuzaki M. The delta2 glutamate receptor gates long-term depression by coordinating interactions between two AMPA receptor phosphorylation sites. Proc Natl Acad Sci U S A. 2013;110(10):E948–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Guastavino JM, Sotelo C, Damez-Kinselle I. Hot-foot murine mutation: behavioral effects and neuroanatomical alterations. Brain Res. 1990;523(2):199–210.

    Article  CAS  PubMed  Google Scholar 

  22. Lalouette A, Lohof A, Sotelo C, Guenet J, Mariani J. Neurobiological effects of a null mutation depend on genetic context: comparison between two hotfoot alleles of the delta-2 ionotropic glutamate receptor. Neuroscience. 2001;105(2):443–55.

    Article  CAS  PubMed  Google Scholar 

  23. Utine GE, Haliloglu G, Salanci B, Cetinkaya A, Kiper PO, Alanay Y, et al. A homozygous deletion in GRID2 causes a human phenotype with cerebellar ataxia and atrophy. J Child Neurol. 2013;28(7):926–32.

    Article  PubMed  Google Scholar 

  24. Hills LB, Masri A, Konno K, Kakegawa W, Lam AT, Lim-Melia E, et al. Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and tonic upgaze in humans. Neurology. 2013;81(16):1378–86.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Maier A, Klopocki EPDRN, Horn DPDM, Tzschach APDM, Holm T, Meyer R, et al. De novo partial deletion in GRID2 presenting with complicated spastic paraplegia. Muscle Nerve. 2014;49(2):289–92.

    Article  CAS  PubMed  Google Scholar 

  26. Coutelier M, Burglen L, Mundwiller E, Abada-Bendib M, Rodriguez D, Chantot-Bastaraud S, et al. GRID2 mutations span from congenital to mild adult-onset cerebellar ataxia. Neurology. 2015;84(17):1751–9.

    Article  CAS  PubMed  Google Scholar 

  27. Lalonde R, Hayzoun K, Selimi F, Mariani J, Strazielle C. Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor. Physiol Behav. 2003;80(2–3):333–9.

    Article  CAS  PubMed  Google Scholar 

  28. Selimi F, Lohof AM, Heitz S, Lalouette A, Jarvis CI, Bailly Y, et al. Lurcher GRID2-induced death and depolarization can be dissociated in cerebellar Purkinje cells. Neuron. 2003;37(5):813–9.

    Article  CAS  PubMed  Google Scholar 

  29. McFarland R, Blokhin A, Sydnor J, Mariani J, Vogel MW. Oxidative stress, nitric oxide, and the mechanisms of cell death in Lurcher Purkinje cells. Dev Neurobiol. 2007;67:1032–46.

    Article  CAS  PubMed  Google Scholar 

  30. McFarland R, Zanjani HS, Mariani J, Vogel MW. Changes in the distribution of the a3 Na+/K+ ATPase subunit in heterozygous Lurcher Purkinje cells as a genetic model of chronic depolarization during development. Int J Cell Biol. 2014

  31. Zanjani HS, Vogel MW, Delhaye-Bouchaud N, Martinou JC, Mariani J. Increased cerebellar Purkinje cell numbers in mice overexpressing a human bcl-2 transgene. J Comp Neurol. 1996;374:332–41.

    Article  CAS  PubMed  Google Scholar 

  32. Wetts R, Herrup K. Cerebellar Purkinje cells are descended from a small number of progenitors committed during early development: quantitative analysis of lurcher chimeric mice. J Neurosci. 1982;2:1494–8.

    CAS  PubMed  Google Scholar 

  33. Herrup K, Sunter K. Cell lineage dependent and independent control of Purkinje cell number in the mammalian CNS: further quantitative studies of lurcher chimeric mice. Dev Biol. 1986;117:417–27.

    Article  CAS  PubMed  Google Scholar 

  34. Hendry IA. A method to correct adequately for the change in neuronal size when estimating neuronal numbers following nerve growth factor treatment. J Neurocytol. 1976;5:337–49.

    Article  CAS  PubMed  Google Scholar 

  35. Wetts R, Herrup K. Interaction of granule, Purkinje and inferior olivary neurons in lurcher chimeric mice. II. Granule cell death. Brain Res. 1982;250:358–63.

    Article  CAS  PubMed  Google Scholar 

  36. Vogel MW, Herrup K. Numerical matching in the mammalian CNS: lack of a competitive advantage of early over late-generated cerebellar granule cells. J Comp Neurol. 1989;283:118–28.

    Article  CAS  PubMed  Google Scholar 

  37. Zanjani HS, Vogel MW, Delhaye-Bouchaud N, Martinou JC, Mariani J. Increased inferior olivary neuron and cerebellar granule cell numbers in transgenic mice overexpressing the human Bcl-2 gene. J Neurobiol. 1997;32(5):502–16.

    Article  CAS  PubMed  Google Scholar 

  38. Fan H, Favero M, Vogel MW. Elimination of Bax expression in mice increases cerebellar Purkinje cell numbers but not the number of granule cells. J Comp Neurol. 2001;436:82–91.

    Article  CAS  PubMed  Google Scholar 

  39. Zanjani H, Lemaigre-Dubreuil Y, Tillakaratne NJ, Blokhin A, McMahon RP, Tobin AJ, et al. Cerebellar Purkinje cell loss in aging Hu-Bcl-2 transgenic mice. J Comp Neurol. 2004;475(4):481–92.

    Article  PubMed  Google Scholar 

  40. Popken GJ, Farel FB. Sensory neuron number in neonatal and adult rats estimated by means of stereologic and profile-based methods. J Comp Neurol. 1997;386:8–15.

    Article  CAS  PubMed  Google Scholar 

  41. Guillery RW, Herrup K. Quantification without pontification: choosing a method for counting objects in sectioned tissues. J Comp Neurol. 1997;386:2–7.

    Article  CAS  PubMed  Google Scholar 

  42. Farel PB. Trust, but verify: the necessity of empirical verification in quantitative neurobiology. Anat Rec. 2002;269(3):157–61.

    Article  PubMed  Google Scholar 

  43. von Bartheld CS. Counting particles in tissue sections: choices of methods and importance of calibration to minimize biases. Histol Histopathol. 2002;17:639–48.

    Google Scholar 

  44. Caddy KWT, Herrup K. Studies of the dendritic tree of wild-type cerebellar Purkinje cells in lurcher chimeric mice. J Comp Neurol. 1990;297:121–31.

    Article  CAS  PubMed  Google Scholar 

  45. Yuzaki M. New (but old) molecules regulating synapse integrity and plasticity: Cbln1 and the delta2 glutamate receptor. Neuroscience. 2009;162(3):633–43.

    Article  CAS  PubMed  Google Scholar 

  46. Yuzaki M. The ins and outs of GluD2—why and how Purkinje cells use the special glutamate receptor. Cerebellum. 2011;11(2):438–9.

    Article  Google Scholar 

  47. Mandolesi G, Autuori E, Cesa R, Premoselli F, Cesare P, Strata P. GluRdelta2 expression in the mature cerebellum of hotfoot mice promotes parallel fiber synaptogenesis and axonal competition. PLoS One. 2009;4(4):e5243.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Mandolesi G, Cesa R, Autuori E, Strata P. An orphan ionotropic glutamate receptor: the delta2 subunit. Neuroscience. 2009;158(1):67–77.

    Article  CAS  PubMed  Google Scholar 

  49. Mishina M, Uemura T, Yasumura M, Yoshida T. Molecular mechanism of parallel fiber-Purkinje cell synapse formation. Front Neural Circuits. 2012;6:90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sarna JR, Hawkes R. Patterned Purkinje cell death in the cerebellum. Prog Neurobiol. 2003;70(6):473–507.

    Article  CAS  PubMed  Google Scholar 

  51. Sotelo C. Cerebellar synaptogenesis: what we can learn from mutant mice. J Exp Biol. 1990;153:225–49.

    CAS  PubMed  Google Scholar 

  52. Doughty ML, De Jager PL, Korsmeyer SJ, Heintz N. Neurodegeneration in Lurcher mice occurs via multiple cell death pathways. J Neurosci. 2000;20(10):3687–94.

    CAS  PubMed  Google Scholar 

  53. Herrup K, Shojaeian-Zanjani H, Panzini L, Sunter K, Mariani J. The numerical matching of source and target populations in the CNS: the inferior olive to Purkinje cell projection. Dev Brain Res. 1996;96:28–35.

    Article  CAS  Google Scholar 

  54. Dahmane N, Ruiz-i-Altaba A. Sonic hedgehog regulates the growth and patterning of the cerebellum. Development. 1999;126(14):3089–100.

    PubMed  Google Scholar 

  55. Herrup K. Role of staggerer gene in determining cell number in cerebellar cortex. I. Granule cell death is an indirect consequence of staggerer gene action. Brain Res. 1983;11:267–74.

    Article  Google Scholar 

  56. Herrup K, Mullen RJ. Staggerer chimeras: intrinsic nature of Purkinje cell defects and implications for normal cerebellar development. Brain Res. 1979;178:443–57.

    Article  CAS  PubMed  Google Scholar 

  57. Herrup K, Sunter K. Numerical matching during cerebellar development: quantitative analysis of granule cell death in staggerer mouse chimeras. J Neurosci. 1987;7:829–36.

    CAS  PubMed  Google Scholar 

  58. Smeyne RJ, Chu T, Lewin A, Bian F, Crisman SS, Kunsch C, et al. Local control of granule cell generation by cerebellar Purkinje cells. Mol Cell Neurosci. 1995;6:230–51.

    Article  CAS  PubMed  Google Scholar 

  59. Sonmez E, Herrup K. Role of staggerer gene in determining cell number in cerebellar cortex. II. Granule cell death and persistence of the external granule cell layer in young mouse chimeras. Brain Res. 1984;12:271–83.

    Article  Google Scholar 

  60. Wallace VA. Purkinje-cell-derived Sonic hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum. Curr Biol. 1999;9(8):445–8.

    Article  CAS  PubMed  Google Scholar 

  61. Vogel MW, Sunter K, Herrup K. Numerical matching between granule and Purkinje cells in lurcher chimeric mice: a hypothesis for the trophic rescue of granule cells from target related cell death. J Neurosci. 1989;9:3454–62.

    CAS  PubMed  Google Scholar 

  62. Wechsler-Reya RJ, Scott MP. Control of neuronal precursor proliferation in the cerebellum by Sonic hedgehog. Neuron. 1999;22(1):103–14.

    Article  CAS  PubMed  Google Scholar 

  63. Wetts R, Herrup K. Direct correlation between Purkinje and granule cell number in the cerebella of lurcher chimeras and wild-type mice. Dev Brain Res. 1983;10:41–7.

    Article  Google Scholar 

  64. Selimi F, Doughty M, Delhaye-Bouchaud N, Mariani J. Target-related and intrinsic neuronal death in Lurcher mutant mice are both mediated by caspase-3 activation. J Neurosci. 2000;20:992–1000.

    CAS  PubMed  Google Scholar 

  65. Rios I, Alvarez-Rodriguez R, Marti E, Pons S. Bmp2 antagonizes sonic hedgehog-mediated proliferation of cerebellar granule neurones through Smad5 signalling. Development. 2004;131(13):3159–68.

    Article  CAS  PubMed  Google Scholar 

  66. Doughty ML, Lohof A, Campana A, Delhaye-Bouchaud N, Mariani J. Neurotrophin-3 promotes cerebellar granule cell exit from the EGL. Eur J Neurosci. 1998;10(9):3007–11.

    Article  CAS  PubMed  Google Scholar 

  67. Williams R, Herrup K. The control of neuron number. Annu Rev Neurosci. 1988;11:423–53.

    Article  CAS  PubMed  Google Scholar 

  68. Bradley PM, Berry M. The Purkinje cell dendritic tree in mutant mouse cerebellum. A quantitative Golgi study of weaver and staggerer mice. Brain Res. 1978;142:135–41.

    Article  CAS  PubMed  Google Scholar 

  69. Hirano A, Dembitzer HB. The fine structure of staggerer cerebellum. J Neuropathol Exp Neurol. 1975;34:1–11.

    Article  CAS  PubMed  Google Scholar 

  70. Landis DMD, Sidman RL. Electron microscopic analysis of postnatal histogenesis in the cerebellar cortex of staggerer mutant mice. J Comp Neurol. 1978;179:831–64.

    Article  CAS  PubMed  Google Scholar 

  71. Sotelo C, Changeux J-P. Transsynaptic degeneration “en cascade” in the cerebellar cortex of staggerer mutant mice. Brain Res. 1974;67:519–26.

    Article  CAS  PubMed  Google Scholar 

  72. Caddy KW, Biscoe TJ. Structural and quantitative studies on the normal C3H and Lurcher mutant mouse. Philos Trans R Soc Lond B Biol Sci. 1979;287(1020):167–201.

    Article  CAS  PubMed  Google Scholar 

  73. Swisher DA, Wilson DB. Cerebellar histogenesis in the Lurcher (Lc) mutant mouse. J Comp Neurol. 1977;173:205–17.

    Article  CAS  PubMed  Google Scholar 

  74. Landis SC, Mullen RJ. The development and degeneration of Purkinje cells in pcd mutant mice. J Comp Neurol. 1978;177(1):125–43.

    Article  CAS  PubMed  Google Scholar 

  75. Mullen RJ, Eicher EM, Sidman RL. Purkinje cell degeneration, a new neurological mutation in the mouse. Proc Natl Acad Sci U S A. 1976;73:208–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Triarhou LC. Biological clues on neuronal degeneration based on theoretical fits of decay patterns: towards a mathematical neuropathology. Folia Neuropathol. 2010;48(1):3–10.

    PubMed  Google Scholar 

  77. Triarhou LC. Rate of neuronal fallout in a transsynaptic cerebellar model. Brain Res Bull. 1998;47(3):219–22.

    Article  CAS  PubMed  Google Scholar 

  78. Kurihara H, Hashimoto K, Kano M, Takayama C, Sakimura K, Mishina M, et al. Impaired parallel fiber→Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor delta2 subunit. J Neurosci. 1997;17:9613–23.

    CAS  PubMed  Google Scholar 

  79. Ichikawa R, Miyazaki T, Kano M, Hashikawa T, Tatsumi H, Sakimura K, et al. Distal extension of climbing fiber territory and multiple innervation caused by aberrant wiring to adjacent spiny branchlets in cerebellar Purkinje cells lacking glutamate receptor delta 2. J Neurosci. 2002;22(19):8487–503.

    CAS  PubMed  Google Scholar 

  80. Yuzaki M. Cerebellar LTD vs. motor learning-Lessons learned from studying GluD2. Neural Netw. 2012;47(2012):36–41.

    PubMed  Google Scholar 

  81. Kaneko M, Yamaguchi K, Eiraku M, Sato M, Takata N, Kiyohara Y, et al. Remodeling of monoplanar Purkinje cell dendrites during cerebellar circuit formation. PLoS One. 2011;6(5):e20108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Metzger F. Molecular and cellular control of dendrite maturation during brain development. Curr Mol Pharmacol. 2009;3(1):1–11.

    Article  Google Scholar 

  83. Tanaka M. Dendrite formation of cerebellar Purkinje cells. Neurochem Res. 2009;34(12):2078–88.

    Article  CAS  PubMed  Google Scholar 

  84. Boukhtouche F, Janmaat S, Vodjdani G, Gautheron V, Mallet J, Dusart I, et al. Retinoid-related orphan receptor alpha controls the early steps of Purkinje cell dendritic differentiation. J Neurosci. 2006;26:1531–8.

    Article  CAS  PubMed  Google Scholar 

  85. Boukhtouche F, Brugg B, Wehrlé R, Bois-Joyeux B, Danan JL, Dusart I, et al. Induction of early Purkinje cell dendritic differentiation by thyroid hormone requires RORα. Neural Dev. 2010;5:18.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Takeo YH, Kakegawa W, Miura E, Yuzaki M. RORa regulates multiple aspects of dendrite development in cerebellar Purkinje cells in vivo. J Neurosci. 2015;35:12518–34.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a UPMC LIA (Laboratoire international associé) grant to JM and by a visiting professor grant of UPMC to MWV. We thank Corinne Nantet for her histological assistance. This article was prepared while MWV was employed at the University of Maryland School of Medicine. The opinions expressed in this article are the authors’ own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the US government.

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Authors and Affiliations

  1. Sorbonne Universités UPMC Univ. Paris 06, IBPS, UMR 8256, Biological Adaptation and Ageing, B2A, 75005, Paris, France

    Hadi S. Zanjani & Jean Mariani

  2. CNRS, UMR 8256, B2A, F-75005, Paris, France

    Hadi S. Zanjani & Jean Mariani

  3. Institut de la Longévité, APHP, DHU Fast, 94205, Ivry-Sur-Seine, France

    Jean Mariani

  4. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD, 21228, USA

    Michael W. Vogel

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Correspondence to Michael W. Vogel.

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Authors’ Contributions

All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Hadi Zanjani, Michael W. Vogel, and Jean Mariani were responsible for the study concept and design; Hadi Zanjani for the acquisition of data; Hadi Zanjani, Michael W. Vogel, and Jean Mariani for the analysis and interpretation of data; Hadi Zanjani and Michael W. Vogel for the drafting of the manuscript; Hadi Zanjani, Michael W. Vogel, and Jean Mariani for the critical revision of the manuscript for intellectual content; Hadi Zanjani and Michael W. Vogel for the statistical analysis; Jean Mariani for the obtained funding; Hadi Zanjani and Jean Mariani for the administrative, technical, and material support; and Hadi Zanjani, Michael W. Vogel, and Jean Mariani for the study supervision.

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Zanjani, H.S., Vogel, M.W. & Mariani, J. Deletion of the GluRδ2 Receptor in the Hotfoot Mouse Mutant Causes Granule Cell Loss, Delayed Purkinje Cell Death, and Reductions in Purkinje Cell Dendritic Tree Area. Cerebellum 15, 755–766 (2016). https://doi.org/10.1007/s12311-015-0748-7

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