Protoplasmic Astrocytes in CA1 Stratum Radiatum Occupy Separate Anatomical Domains
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Protoplasmic astrocytes are increasingly thought to interact extensively with neuronal elements in the brain and to influence their activity. Recent reports have also begun to suggest that physiologically, and perhaps functionally, diverse forms of these cells may be present in the CNS. Our current understanding of astrocyte form and distribution is based predominately on studies that used the astrocytic marker glial fibrillary acidic protein (GFAP) and on studies using metal-impregnation techniques. The prevalent opinion, based on studies using these methods, is that astrocytic processes overlap extensively and primarily share the underlying neuropil. However, both of these techniques have serious shortcomings for visualizing the interactions among these structurally complex cells. In the present study, intracellular injection combined with immunohistochemistry for GFAP show that GFAP delineates only ∼15% of the total volume of the astrocyte. As a result, GFAP-based images have led to incorrect conclusions regarding the interaction of processes of neighboring astrocytes. To investigate these interactions in detail, groups of adjacent protoplasmic astrocytes in the CA1 stratum radiatum were injected with fluorescent intracellular tracers of distinctive emissive wavelengths and analyzed using three-dimensional (3D) confocal analysis and electron microscopy. Our findings show that protoplasmic astrocytes establish primarily exclusive territories. The knowledge of how the complex morphology of protoplasmic astrocytes affects their 3D relationships with other astrocytes, oligodendroglia, neurons, and vasculature of the brain should have important implications for our understanding of nervous system function.
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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 [395]
In “Astrocyte heterogeneity and anatomical domains” (page unavailable), the paper estimates that an astrocyte in adult rat CA1 would oversee approximately 140,000 synapses, broadly consistent with about 10^5, but it does not establish that each synapse is enwrapped. In “Spatial relationships between neighboring protoplasmic astrocytes” (page unavailable), it says nearly every astrocyte forms end-feet with at least one blood vessel; it does not give an upper limit of four capillaries or say that an astrocyte enwraps about four neuronal cell bodies. (LLM, conf=0.87)
Experimental — accuracy not yet measuredGq-DREADD expression remained restricted to astrocytes based on co-localization with GFAP and morphology consistent with astrocytic immunoreactivity patterns.
“Histological visualization with the fluorescent reporter mCherry confirmed that Gq-DREADD expression remained restricted to astrocytes based on their co-localization with the astrocyte marker GFAP (Figure 1C) and morphology consistent with astrocytic immunoreactivity patterns (Benediktsson et al., 2005;Bushong et al., 2002;Scofield et al., 2015).”
From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Bushong et al., 2002
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Horii-Hayashi, N., Tatsumi, K., Matsusue, Y., Okuda, H., Okuda, A., Hayashi, M., Yano, H., Tsuboi, A., Nishi, M., Yoshikawa, M., et al. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.07.064 · Cited by 16 · see citing works
Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
Bougnères, P., & Le Stunff, C. (2025) · Genes · doi:10.3390/genes16050590 · Cited by 11 · see citing works
Philtjens, S., Turnbull, M. T., Thedy, B. P., Moon, Y., & Kim, J. (2020) · doi:10.1101/2020.04.27.064881 · Cited by 7 · see citing works
“…mCherry confirmed that Gq-DREADD expression remained restricted to astrocytes based on their co-localization with the astrocyte marker GFAP (Figure 1C) and morphology consistent with astrocytic immunoreactivity patterns (Benediktsson et al., 2005; Bushong et al., 2002; Scofield et al., 2015).”
Background
- Authors
- Bushong, E. A., Martone, M. E., Jones, Y. Z., & Ellisman, M. H.
- Affiliations
- University of California San Diego (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-01-01
- Volume
- 22
- Issue
- 1
- Pages
- 183-192
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6757596
- OpenAlex
- W2129567809
- Cited by
- 1,578
- References
- 2
- Citations by year
- 2026: 43 · 2025: 86 · 2024: 78 · 2023: 110 · 2022: 80 · 2021: 109 · 2020: 93 · 2019: 73 · 2018: 68 · 2017: 71 · 2016: 72 · 2015: 79 · 2014: 97 · 2013: 76 · 2012: 59
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health (5r01dc003192-05, RR 04050)
- National Institute on Deafness and Other Communication Disorders (DC03192)
- National Center for Research Resources (RR 04050, P41RR004050)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Anatomy › Medical and Biological Sciences
- Keywords
- protoplasmic astrocyte, CA1 stratum radiatum, astrocyte morphology, glial fibrillary acidic protein, astrocyte-neuron interaction, oligodendroglia, hippocampus
- MeSH terms
- Animals, Astrocytes, Cytoplasm, Fluorescent Dyes, Glial Fibrillary Acidic Protein, Hippocampus, Immunohistochemistry, Iontophoresis, Isoquinolines, Male, Microscopy, Electron, Oxidation-Reduction, Photochemistry, Rats, Sprague-Dawley, Microscopy, Confocal, Cell Size, Rats
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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