α-Synuclein Expression in the Mouse Cerebellum Is Restricted to VGluT1 Excitatory Terminals and Is Enriched in Unipolar Brush Cells

Sun Kyong Lee, Roy V. Sillitoe, Coralie Silva, Marco Martina, Gabriella Sekerkova*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

α-Synuclein has a crucial role in synaptic vesicle release and synaptic membrane recycling. Although its general expression pattern has been described in the cerebellum, the precise cerebellar structures where α-synuclein is localized are poorly understood. To address this question, we used α-synuclein immunohistochemistry in adult mice cerebellar sections. We found that α-synuclein labels glutamatergic but not glycinergic and GABAergic synaptic terminals in the molecular and granule cell layers. α-Synuclein was preferentially expressed in parallel and mossy fiber synaptic terminals that also express vesicular glutamate transporter 1 (VGluT1), while it was not detected in VGluT2-positive climbing fibers. α-Synuclein was particularly enriched in lobules IX and X, a region known to contain a high density of unipolar brush cells (UBCs). To elucidate whether the α-synuclein-positive mossy fibers belong to UBCs, we double-labeled cerebellar sections with antibodies to α-synuclein and UBC-type-specific markers (calretinin for type I and metabotropic glutamate receptor 1α (mGluR1α) for type II UBCs) and took advantage of organotypic cerebellar cultures (in which all mossy fibers are UBC axons) and moonwalker mice (in which almost all UBCs are ablated) and found that both type I and type II UBCs express α-synuclein. In moonwalker mutant cerebella, the α-synuclein/VGluT1 immunolabeling showed a dramatic decrease in the vestibulocerebellum that correlated with the absence of UBC. α-Synuclein appears to be an excellent marker for intrinsic mossy fibers of the VGluT1 subset in conjunction with UBCs of both subtypes.

Original languageEnglish (US)
Pages (from-to)516-527
Number of pages12
JournalCerebellum
Volume14
Issue number5
DOIs
StatePublished - Oct 1 2015

Fingerprint

Vesicular Glutamate Transport Protein 1
Synucleins
Cerebellum
Presynaptic Terminals
Calbindin 2
Synaptic Membranes
Synaptic Vesicles

Keywords

  • Granule cells
  • Moonwalker mice
  • Mossy fiber terminals
  • VGluT1
  • VGluT2
  • Vestibulocerebellum

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

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title = "α-Synuclein Expression in the Mouse Cerebellum Is Restricted to VGluT1 Excitatory Terminals and Is Enriched in Unipolar Brush Cells",
abstract = "α-Synuclein has a crucial role in synaptic vesicle release and synaptic membrane recycling. Although its general expression pattern has been described in the cerebellum, the precise cerebellar structures where α-synuclein is localized are poorly understood. To address this question, we used α-synuclein immunohistochemistry in adult mice cerebellar sections. We found that α-synuclein labels glutamatergic but not glycinergic and GABAergic synaptic terminals in the molecular and granule cell layers. α-Synuclein was preferentially expressed in parallel and mossy fiber synaptic terminals that also express vesicular glutamate transporter 1 (VGluT1), while it was not detected in VGluT2-positive climbing fibers. α-Synuclein was particularly enriched in lobules IX and X, a region known to contain a high density of unipolar brush cells (UBCs). To elucidate whether the α-synuclein-positive mossy fibers belong to UBCs, we double-labeled cerebellar sections with antibodies to α-synuclein and UBC-type-specific markers (calretinin for type I and metabotropic glutamate receptor 1α (mGluR1α) for type II UBCs) and took advantage of organotypic cerebellar cultures (in which all mossy fibers are UBC axons) and moonwalker mice (in which almost all UBCs are ablated) and found that both type I and type II UBCs express α-synuclein. In moonwalker mutant cerebella, the α-synuclein/VGluT1 immunolabeling showed a dramatic decrease in the vestibulocerebellum that correlated with the absence of UBC. α-Synuclein appears to be an excellent marker for intrinsic mossy fibers of the VGluT1 subset in conjunction with UBCs of both subtypes.",
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α-Synuclein Expression in the Mouse Cerebellum Is Restricted to VGluT1 Excitatory Terminals and Is Enriched in Unipolar Brush Cells. / Lee, Sun Kyong; Sillitoe, Roy V.; Silva, Coralie; Martina, Marco; Sekerkova, Gabriella.

In: Cerebellum, Vol. 14, No. 5, 01.10.2015, p. 516-527.

Research output: Contribution to journalArticle

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