ArticleBiophysical journal2002
Asymmetry of glia near central synapses favors presynaptically directed glutamate escape.
Article in Biophysical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 149 citations in OpenAlex.
- Perisynaptic Astrocytic Processes as Communication Hubs and Early Sites of Dysfunction.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- Central amygdala astrocyte plasticity underlies GABAergic dysregulation in ethanol dependence.Translational psychiatry · 2025Article
- Astrocyte Kir4.1 expression level territorially controls excitatory transmission in the brain.Cell reports · 2025Article
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- Astrocyte coverage of excitatory synapses correlates to measures of synapse structure and function in primary visual cortex.bioRxiv : the preprint server for biology · 2023Article
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- Asymmetric dysregulation of glutamate dynamics across the synaptic cleft in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2023Article
- Astrocyte regulation of synaptic signaling in psychiatric disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Glial Cell Modulation of Dendritic Spine Structure and Synaptic Function.Advances in neurobiology · 2023Review
- Honey, I shrunk the extracellular space: Measurements and mechanisms of astrocyte swelling.Glia · 2022Review
- Review
- Regulation of glutamate homeostasis in the nucleus accumbens by astrocytic CB1 receptors and its role in cocaine-motivated behaviors.Addiction neuroscience · 2022Article
- Plasticity in astrocyte subpopulations regulates heroin relapse.Science advances · 2022Article
- KGlia · 2022Article
- Photonics tools begin to clarify astrocyte calcium transients.Neurophotonics · 2022Review
- Estimating the glutamate transporter surface density in distinct sub-cellular compartments of mouse hippocampal astrocytes.PLoS computational biology · 2022Article
- Extrasynaptic therapeutic targets in substance use and stress disorders.Trends in pharmacological sciences · 2022Review
- Looking to the stars for answers: Strategies for determining how astrocytes influence neuronal activity.Computational and structural biotechnology journal · 2022Review
- Accumbens D2-MSN hyperactivity drives antipsychotic-induced behavioral supersensitivity.Molecular psychiatry · 2021Article
- Astrocytes as cellular mediators of cue reactivity in addiction.Current opinion in pharmacology · 2021Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent findings demonstrate that synaptically released excitatory neurotransmitter glutamate activates receptors outside the immediate synaptic cleft and that the extent of such extrasynaptic actions is regulated by the high affinity glutamate uptake. The bulk of glutamate transporter systems are evenly distributed in the synaptic neuropil, and it is generally assumed that glutamate escaping the cleft affects pre- and postsynaptic receptors to a similar degree. To test whether this is indeed the case, we use quantitative electron microscopy and establish the stochastic pattern of glial occurrence in the three-dimensional (3D) vicinity of two common types of excitatory central synapses, stratum radiatum synapses in hippocampus and parallel fiber synapses in cerebellum. We find that the occurrence of glia postsynaptically is strikingly higher (3-4-fold) than presynaptically, in both types of synapses. To address the functional consequences of this asymmetry, we simulate diffusion and transport of synaptically released glutamate in these two brain areas using a detailed 3D compartmental model of the extracellular space with glutamate transporters arranged unevenly, in accordance with the obtained experimental data. The results predict that glutamate escaping the synaptic cleft is 2-4 times more likely to activate presynaptic compared to postsynaptic receptors. Simulations also show that postsynaptic neuronal transporters (EAAT4 type) at dendritic spines of cerebellar Purkinje cells exaggerate this asymmetry further. Our data suggest that the perisynaptic environment of these common central synapses favors fast presynaptic feedback in the information flow while preserving the specificity of the postsynaptic input.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.