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

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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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Acknowledgments

This study was funded by NIH grant NS09904 (MM), U54HD083092 (RVS), and NS089664 (RVS). The BCM IDDRC Neuropathology Core performed a portion of the staining experiments. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, Feinberg School of Medicine, Northwestern University, Morton 5-619, Chicago, IL, 60611, USA

    Sun Kyong Lee, Coralie Silva, Marco Martina & Gabriella Sekerkova

  2. Department of Pathology and Immunology, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute of Texas Children’s Hospital, Houston, TX, 77030, USA

    Roy V. Sillitoe

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  1. Sun Kyong Lee
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Correspondence to Gabriella Sekerkova.

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This paper is dedicated to the Prof. Enrico Mugnaini, a visionary neuroanatomist and an inspirational mentor.

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Lee, S.K., Sillitoe, R.V., Silva, C. et al. α-Synuclein Expression in the Mouse Cerebellum Is Restricted to VGluT1 Excitatory Terminals and Is Enriched in Unipolar Brush Cells. Cerebellum 14, 516–527 (2015). https://doi.org/10.1007/s12311-015-0673-9

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