ArticleProceedings of the National Academy of Sciences of the United States of America2017
Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 73 citations in OpenAlex.
- Molecular and Cellular Mechanisms of Synaptogenesis and Synaptic Refinement During Cerebellar Circuit Formation.International journal of molecular sciences · 2026Review
- Cerebellar astrocytic alterations in depression.Translational psychiatry · 2026Article
- mGluR1 signaling is necessary for strengthening winner climbing fiber inputs in the developing mouse cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synaptic transmission is dispensable for selecting the winner input but is crucial for the subsequent events of synapse elimination.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Effect of Glutamate Antibodies on ASCL1 Gene Expression in Aging Mice with Spatial Memory Impairment Caused by Amyloid Fibrils of the Proinflammatory Protein S100A9.Bulletin of experimental biology and medicine · 2025Article
- Ultrastructural characterization of peri-synaptic astrocytic processes around cerebellar Purkinje spines under resting and stimulated conditions.Molecular brain · 2025Article
- Distribution and morphological features of astrocytes and Purkinje cells in the human cerebellum.Frontiers in neuroanatomy · 2025Article
- Astrocytic Neuroligin-3 influences gene expression and social behavior, but is dispensable for synapse number.Molecular psychiatry · 2025Article
- Nasal obstruction during development leads to defective synapse elimination, hypersynchrony, and impaired cerebellar function.Communications biology · 2024Article
- The Interplay between Neurotransmitters and Calcium Dynamics in Retinal Synapses during Development, Health, and Disease.International journal of molecular sciences · 2024Review
- Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation.Nature communications · 2024Article
- Molecular and cellular mechanisms of developmental synapse elimination in the cerebellum: Involvement of autism spectrum disorder-related genes.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2024Review
- Article
- Altered calcium signaling in Bergmann glia contributes to spinocerebellar ataxia type-1 in a mouse model of SCA1.Neurobiology of disease · 2023Article
- C1ql1-Bai3 signaling is necessary for climbing fiber synapse formation in mature Purkinje cells in coordination with neuronal activity.Molecular brain · 2023Article
- Glioma epileptiform activity and progression are driven by IGSF3-mediated potassium dysregulation.Neuron · 2023Article
- Aryl Hydrocarbon Receptor in Glia Cells: A Plausible Glutamatergic Neurotransmission Orchestrator.Neurotoxicity research · 2023Review
- Astrocytic modulation of neuronal signalling.Frontiers in network physiology · 2023Review
- Spatial and Temporal Diversity of Astrocyte Phenotypes in Spinocerebellar Ataxia Type 1 Mice.Cells · 2022Article
- Review
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9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 from PC 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.
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