Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells

Taisuke Miyazaki, Miwako Yamasaki, Kouichi Hashimoto, Kazuhisa Kohda, Michisuke Yuzaki, Keiko Shimamoto, Kohichi Tanaka, Masanobu Kano, Masahiko Watanabe

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Astrocytes regulate synaptic transmission through controlling neurotransmitter concentrations around synapses. Little is known, however, about their roles in neural circuit development. Here we report that Bergmann glia (BG), specialized cerebellar astrocytes that thoroughly enwrap Purkinje cells (PCs), are essential for synaptic organization in PCs through the action of the L-glutamate/L-aspartate transporter (GLAST). In GLAST-knockout mice, dendritic innervation by the main ascending climbing fiber (CF) branch was significantly weakened, whereas the transverse branch, which is thin and nonsynaptogenic in control mice, was transformed into thick and synaptogenic branches. Both types of CF branches frequently produced aberrant wiring to proximal and distal dendrites, causing multiple CF-PC innervation. Our electrophysiological analysis revealed that slow and small CF-evoked excitatory postsynaptic currents (EPSCs) were recorded from almost all PCs in GLAST-knockout mice. These atypical CF-EPSCs were far more numerous and had significantly faster 10-90% rise time than those elicited by glutamate spillover under pharmacological blockade of glial glutamate transporters. Innervation by parallel fibers (PFs) was also affected. PF synapses were robustly increased in the entire dendritic trees, leading to impaired segregation of CF and PF territories. Furthermore, lamellate BG processes were retracted fromPC dendrites and synapses, leading to the exposure of these neuronal elements to the extracellular milieus. These synaptic and glial phenotypes were reproduced in wild-type mice after functional blockade of glial glutamate transporters. These findings highlight that glutamate transporter function by GLAST on BG plays important roles in development and maintenance of proper synaptic wiring and wrapping in PCs.

Original languageEnglish
Pages (from-to)7438-7443
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number28
DOIs
Publication statusPublished - 2017 Jul 11

Fingerprint

Amino Acid Transport System X-AG
Purkinje Cells
Aspartic Acid
Neuroglia
Glutamic Acid
Synapses
Excitatory Postsynaptic Potentials
Dendrites
Knockout Mice
Astrocytes
Synaptic Transmission
Neurotransmitter Agents
Maintenance
Pharmacology
Phenotype

Keywords

  • Bergmann glia
  • Climbing fiber
  • Glutamate transporter
  • Parallel fiber
  • Purkinje cell

ASJC Scopus subject areas

  • General

Cite this

Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells. / Miyazaki, Taisuke; Yamasaki, Miwako; Hashimoto, Kouichi; Kohda, Kazuhisa; Yuzaki, Michisuke; Shimamoto, Keiko; Tanaka, Kohichi; Kano, Masanobu; Watanabe, Masahiko.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 28, 11.07.2017, p. 7438-7443.

Research output: Contribution to journalArticle

Miyazaki, Taisuke ; Yamasaki, Miwako ; Hashimoto, Kouichi ; Kohda, Kazuhisa ; Yuzaki, Michisuke ; Shimamoto, Keiko ; Tanaka, Kohichi ; Kano, Masanobu ; Watanabe, Masahiko. / Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 28. pp. 7438-7443.
@article{7e171319199148b4aa55fd89c4693375,
title = "Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells",
abstract = "Astrocytes regulate synaptic transmission through controlling neurotransmitter concentrations around synapses. Little is known, however, about their roles in neural circuit development. Here we report that Bergmann glia (BG), specialized cerebellar astrocytes that thoroughly enwrap Purkinje cells (PCs), are essential for synaptic organization in PCs through the action of the L-glutamate/L-aspartate transporter (GLAST). In GLAST-knockout mice, dendritic innervation by the main ascending climbing fiber (CF) branch was significantly weakened, whereas the transverse branch, which is thin and nonsynaptogenic in control mice, was transformed into thick and synaptogenic branches. Both types of CF branches frequently produced aberrant wiring to proximal and distal dendrites, causing multiple CF-PC innervation. Our electrophysiological analysis revealed that slow and small CF-evoked excitatory postsynaptic currents (EPSCs) were recorded from almost all PCs in GLAST-knockout mice. These atypical CF-EPSCs were far more numerous and had significantly faster 10-90{\%} rise time than those elicited by glutamate spillover under pharmacological blockade of glial glutamate transporters. Innervation by parallel fibers (PFs) was also affected. PF synapses were robustly increased in the entire dendritic trees, leading to impaired segregation of CF and PF territories. Furthermore, lamellate BG processes were retracted fromPC dendrites and synapses, leading to the exposure of these neuronal elements to the extracellular milieus. These synaptic and glial phenotypes were reproduced in wild-type mice after functional blockade of glial glutamate transporters. These findings highlight that glutamate transporter function by GLAST on BG plays important roles in development and maintenance of proper synaptic wiring and wrapping in PCs.",
keywords = "Bergmann glia, Climbing fiber, Glutamate transporter, Parallel fiber, Purkinje cell",
author = "Taisuke Miyazaki and Miwako Yamasaki and Kouichi Hashimoto and Kazuhisa Kohda and Michisuke Yuzaki and Keiko Shimamoto and Kohichi Tanaka and Masanobu Kano and Masahiko Watanabe",
year = "2017",
month = "7",
day = "11",
doi = "10.1073/pnas.1617330114",
language = "English",
volume = "114",
pages = "7438--7443",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "28",

}

TY - JOUR

T1 - Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells

AU - Miyazaki, Taisuke

AU - Yamasaki, Miwako

AU - Hashimoto, Kouichi

AU - Kohda, Kazuhisa

AU - Yuzaki, Michisuke

AU - Shimamoto, Keiko

AU - Tanaka, Kohichi

AU - Kano, Masanobu

AU - Watanabe, Masahiko

PY - 2017/7/11

Y1 - 2017/7/11

N2 - Astrocytes regulate synaptic transmission through controlling neurotransmitter concentrations around synapses. Little is known, however, about their roles in neural circuit development. Here we report that Bergmann glia (BG), specialized cerebellar astrocytes that thoroughly enwrap Purkinje cells (PCs), are essential for synaptic organization in PCs through the action of the L-glutamate/L-aspartate transporter (GLAST). In GLAST-knockout mice, dendritic innervation by the main ascending climbing fiber (CF) branch was significantly weakened, whereas the transverse branch, which is thin and nonsynaptogenic in control mice, was transformed into thick and synaptogenic branches. Both types of CF branches frequently produced aberrant wiring to proximal and distal dendrites, causing multiple CF-PC innervation. Our electrophysiological analysis revealed that slow and small CF-evoked excitatory postsynaptic currents (EPSCs) were recorded from almost all PCs in GLAST-knockout mice. These atypical CF-EPSCs were far more numerous and had significantly faster 10-90% rise time than those elicited by glutamate spillover under pharmacological blockade of glial glutamate transporters. Innervation by parallel fibers (PFs) was also affected. PF synapses were robustly increased in the entire dendritic trees, leading to impaired segregation of CF and PF territories. Furthermore, lamellate BG processes were retracted fromPC dendrites and synapses, leading to the exposure of these neuronal elements to the extracellular milieus. These synaptic and glial phenotypes were reproduced in wild-type mice after functional blockade of glial glutamate transporters. These findings highlight that glutamate transporter function by GLAST on BG plays important roles in development and maintenance of proper synaptic wiring and wrapping in PCs.

AB - Astrocytes regulate synaptic transmission through controlling neurotransmitter concentrations around synapses. Little is known, however, about their roles in neural circuit development. Here we report that Bergmann glia (BG), specialized cerebellar astrocytes that thoroughly enwrap Purkinje cells (PCs), are essential for synaptic organization in PCs through the action of the L-glutamate/L-aspartate transporter (GLAST). In GLAST-knockout mice, dendritic innervation by the main ascending climbing fiber (CF) branch was significantly weakened, whereas the transverse branch, which is thin and nonsynaptogenic in control mice, was transformed into thick and synaptogenic branches. Both types of CF branches frequently produced aberrant wiring to proximal and distal dendrites, causing multiple CF-PC innervation. Our electrophysiological analysis revealed that slow and small CF-evoked excitatory postsynaptic currents (EPSCs) were recorded from almost all PCs in GLAST-knockout mice. These atypical CF-EPSCs were far more numerous and had significantly faster 10-90% rise time than those elicited by glutamate spillover under pharmacological blockade of glial glutamate transporters. Innervation by parallel fibers (PFs) was also affected. PF synapses were robustly increased in the entire dendritic trees, leading to impaired segregation of CF and PF territories. Furthermore, lamellate BG processes were retracted fromPC dendrites and synapses, leading to the exposure of these neuronal elements to the extracellular milieus. These synaptic and glial phenotypes were reproduced in wild-type mice after functional blockade of glial glutamate transporters. These findings highlight that glutamate transporter function by GLAST on BG plays important roles in development and maintenance of proper synaptic wiring and wrapping in PCs.

KW - Bergmann glia

KW - Climbing fiber

KW - Glutamate transporter

KW - Parallel fiber

KW - Purkinje cell

UR - http://www.scopus.com/inward/record.url?scp=85023200389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023200389&partnerID=8YFLogxK

U2 - 10.1073/pnas.1617330114

DO - 10.1073/pnas.1617330114

M3 - Article

C2 - 28655840

AN - SCOPUS:85023200389

VL - 114

SP - 7438

EP - 7443

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 28

ER -