Synaptic Islands Defined by the Territory of a Single Astrocyte
Open accessAbstract
In the mammalian brain, astrocytes modulate neuronal function, in part, by synchronizing neuronal firing and coordinating synaptic networks. Little, however, is known about how this is accomplished from a structural standpoint. To investigate the structural basis of astrocyte-mediated neuronal synchrony and synaptic coordination, the three-dimensional relationships between cortical astrocytes and neurons was investigated. Using a transgenic and viral approach to label astrocytes with enhanced green fluorescent protein, we performed a three-dimensional reconstruction of astrocytes from tissue sections or live animals in vivo. We found that cortical astrocytes occupy nonoverlapping territories similar to those described in the hippocampus. Using immunofluorescence labeling of neuronal somata, a single astrocyte enwraps on average four neuronal somata with an upper limit of eight. Single-neuron dye-fills allowed us to estimate that one astrocyte contacts 300-600 neuronal dendrites. Together with the recent findings showing that glial Ca2+ signaling is restricted to individual astrocytes in vivo, and that Ca2+ signaling leads to gliotransmission, we propose the concept of functional islands of synapses in which groups of synapses confined within the boundaries of an individual astrocyte are modulated by the gliotransmitter environment controlled by that astrocyte. Our description offers a new structurally based conceptual framework to evaluate functional data involving interactions between neurons and astrocytes in the mammalian brain.
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Each astrocyte is in contact with up to four capillaries and enwraps about four neuronal cell bodies and 105 synapses.
“Interposed between neurons and the vasculature, each astrocyte is in contact with up to four capillaries and enwraps about four neuronal cell bodies and 105 synapses [395,396,397].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [397]
The section ‘Single astrocytes enwrap multiple neuronal cell bodies’ reports an average of four neuronal somata per cortical astrocyte. The Introduction reports that a hippocampal astrocyte can contact more than 100,000 synapses, citing earlier work; it does not establish that number for each astrocyte. No passage found supports contact with up to four capillaries. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAt the microscale, an entire astrocyte activates and may exert coordinated influence on synaptic ensembles in its territory.
“second, a microscale, on the order of a single astrocyte, at which the entire cell activates and may exert a coordinated influence on synaptic ensembles residing in its territory 29, 129”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [129]
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- Authors
- Halassa, M. M., Fellin, T., Takano, H., Dong, J.-H., & Haydon, P. G.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Haydon, P. G.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-06-13
- Volume
- 27
- Issue
- 24
- Pages
- 6473-6477
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672436
- OpenAlex
- W2032730787
- Cited by
- 767
- References
- 23
- Citations by year
- 2026: 18 · 2025: 40 · 2024: 36 · 2023: 48 · 2022: 45 · 2021: 56 · 2020: 50 · 2019: 44 · 2018: 35 · 2017: 42 · 2016: 55 · 2015: 33 · 2014: 40 · 2013: 36 · 2012: 39
- FWCI
- 13.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (P20MH071705, MH071705)
- National Institute of Neurological Disorders and Stroke (NS-047321, NS-043142, NS-037585, NS054770, R01NS054770, R01NS037585, R37NS037585, R01NS043142, P30NS047321)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- astrocytes, astrocyte-neuron interaction, neuronal synchronization, 3D reconstruction, gliotransmission, cortical astrocytes, neuronal somata
- MeSH terms
- Animals, Astrocytes, Cell Communication, Cerebral Cortex, Dendrites, Glial Fibrillary Acidic Protein, Humans, Mice, Transgenic, Synaptic Transmission, Neurons, Synapses, Transduction, Genetic, Imaging, Three-Dimensional, Green Fluorescent Proteins, Vesicle-Associated Membrane Protein 2, Mice, In Vitro Techniques
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