ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
Climbing Fiber-Mediated Spillover Transmission to Interneurons Is Regulated by EAAT4.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Glutamate concentration tunes AMPA receptor function through conductance-state occupancy.Nature neuroscience · 2026Article
- Specialized outputs and behavioral contributions of Purkinje cell subtypes.bioRxiv : the preprint server for biology · 2026Article
- Article
- Ethanol disrupts cerebellar synaptic modulation by enhancing EAAT4-mediated glutamate uptake.Communications biology · 2026Article
- Coordination of spike timing among the neurons of the cerebellum.Research square · 2026Article
- Coordination of spike timing among the neurons of the cerebellum.bioRxiv : the preprint server for biology · 2025Article
- Climbing fibers selectively recruit disinhibitory interneurons to enhance dendritic calcium signaling in cerebellar Purkinje cells.bioRxiv : the preprint server for biology · 2025Article
- Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.Neurochemical research · 2025Review
- Pleiotropic neurotransmitters: neurotransmitter-receptor crosstalk regulates excitation-inhibition balance in social brain functions and pathologies.Frontiers in neuroscience · 2025Review
- Afferent convergence to a shared population of interneuron AMPA receptors.Nature communications · 2023Article
- Synchronous spiking of cerebellar Purkinje cells during control of movements.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Heterogeneity of intrinsic plasticity in cerebellar Purkinje cells linked with cortical molecular zones.iScience · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Neurotransmitter spillover is a form of communication not readily predicted by anatomic structure. In the cerebellum, glutamate spillover from climbing fibers recruits molecular layer interneurons in the absence of conventional synaptic connections. Spillover-mediated signaling is typically limited by transporters that bind and reuptake glutamate. Here, we show that patterned expression of the excitatory amino acid transporter 4 (EAAT4) in Purkinje cells regulates glutamate spillover to molecular layer interneurons. Using male and female Aldolase C-Venus knock-in mice to visualize zebrin microzones, we find larger climbing fiber-evoked spillover EPSCs in regions with low levels of EAAT4 compared with regions with high EAAT4. This difference is not explained by presynaptic glutamate release properties or postsynaptic receptor density but rather by differences in the glutamate concentration reaching receptors on interneurons. Inhibiting glutamate transport normalizes the differences between microzones, suggesting that heterogeneity in EAAT4 expression is a primary determinant of differential spillover. These results show that neuronal glutamate transporters limit extrasynaptic transmission in a non-cell-autonomous manner and provide new insight into the functional specialization of cerebellar microzones.
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Registered trials
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