Astroglial networks scale synaptic activity and plasticity
Open accessAbstract
Astrocytes dynamically interact with neurons to regulate synaptic transmission. Although the gap junction proteins connexin 30 (Cx30) and connexin 43 (Cx43) mediate the extensive network organization of astrocytes, their role in synaptic physiology is unknown. Here we show, by inactivating Cx30 and Cx43 genes, that astroglial networks tone down hippocampal synaptic transmission in CA1 pyramidal neurons. Gap junctional networking facilitates extracellular glutamate and potassium removal during synaptic activity through modulation of astroglial clearance rate and extracellular space volume. This regulation limits neuronal excitability, release probability, and insertion of postsynaptic AMPA receptors, silencing synapses. By controlling synaptic strength, connexins play an important role in synaptic plasticity. Altogether, these results establish connexins as critical proteins for extracellular homeostasis, important for the formation of functional synapses.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Astrocytes remove excitatory neurotransmitters and electrolytes from extracellular space, controlling neuronal excitability and enabling synaptic plasticity.
“Astrocytes also remove excitatory neurotransmitters (eg, glutamate) and electrolytes (eg, potassium) from the extracellular space, thus controlling neuronal excitability and enabling synaptic plasticity.62”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [62]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Tripartite synapses: astrocytes process and control synaptic information
Perea, G., Navarrete, M., & Araque, A. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.05.001 · Cited by 1,820 · see citing works
The self-tuning neuron: synaptic scaling of excitatory synapses
Turrigiano, G. G. (2008) · Cell · doi:10.1016/j.cell.2008.10.008 · Cited by 1,533 · see citing works
Evidence for silent synapses: Implications for the expression of LTP
Isaac, J. T. R., Nicoll, R. A., & Malenka, R. C. (1995) · Neuron · doi:10.1016/0896-6273(95)90046-2 · Cited by 1,233 · see citing works
Three-Dimensional Relationships between Hippocampal Synapses and Astrocytes
Ventura, R., & Harris, K. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-16-06897.1999 · Cited by 900 · see citing works
Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission
Rouach, N., Koulakoff, A., Abudara, V., Willecke, K., & Giaume, C. (2008) · Science · doi:10.1126/science.1164022 · Cited by 861 · see citing works
Self-citationAstroglial networks: a step further in neuroglial and gliovascular interactions
Giaume, C., Koulakoff, A., Roux, L., Holcman, D., & Rouach, N. (2010) · Nature reviews. Neuroscience · doi:10.1038/nrn2757 · Cited by 781 · see citing works
Self-citationDjukic, B., Casper, K. B., Philpot, B. D., Chin, L., & McCarthy, K. D. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0723-07.2007 · Cited by 623 · see citing works
Silent synapses and the emergence of a postsynaptic mechanism for LTP
Kerchner, G. A., & Nicoll, R. A. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2501 · Cited by 602 · see citing works
The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus
Wallraff, A., Köhling, R., Heinemann, U., Theis, M., Willecke, K., & Steinhäuser, C. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0037-06.2006 · Cited by 582 · see citing works
Ehrlich, I., & Malinow, R. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4733-03.2004 · Cited by 567 · see citing works
Asztély, F., Erdemli, G., & Kullmann, D. M. (1997) · Neuron · doi:10.1016/s0896-6273(00)80268-8 · Cited by 417 · see citing works
Glia-Synapse Interaction Through Ca2+-Permeable AMPA Receptors in Bergmann Glia
Iino, M., Goto, K., Kakegawa, W., Okado, H., Sudo, M., Ishiuchi, S., Miwa, A., Takayasu, Y., Saito, I., Tsuzuki, K., et al. (2001) · Science · doi:10.1126/science.1058827 · Cited by 392 · see citing works
Glial contributions to excitatory neurotransmission in cultured hippocampal cells
Mennerick, S. J., & Zorumski, C. F. (1994) · Nature · doi:10.1038/368059a0 · Cited by 352 · see citing works
Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential
Teubner, B. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg001 · Cited by 350 · see citing works
Stein, V., House, D. R. C., Bredt, D. S., & Nicoll, R. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-13-05503.2003 · Cited by 341 · see citing works
PSD‐95 regulates synaptic transmission and plasticity in rat cerebral cortex
Béïque, J.-C., & Andrade, R. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.031369 · Cited by 313 · see citing works
Theis, M., Jauch, R., Zhuo, L., Speidel, D., Wallraff, A., Döring, B., Frisch, C., Söhl, G., Teubner, B., Euwens, C., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-03-00766.2003 · Cited by 269 · see citing works
Diamond, J. S. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-21-08328.2001 · Cited by 255 · see citing works
Lutz, S. E., Zhao, Y., Gulinello, M. E., Lee, S. C., Raine, C. S., & Brosnan, C. F. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0341-09.2009 · Cited by 228 · see citing works
Amzica, F., Massimini, M., & Manfridi, A. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-01042.2002 · Cited by 198 · see citing works
BK potassium channels control transmitter release at CA3–CA3 synapses in the rat hippocampus
Raffaelli, G., Saviane, C., Mohajerani, M. H., Pedarzani, P., & Cherubini, E. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.062661 · Cited by 191 · see citing works
Isolation of Current Components and Partial Reaction Cycles in the Glial Glutamate Transporter EAAT2
Otis, T. S., & Kavanaugh, M. P. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-08-02749.2000 · Cited by 164 · see citing works
Diamond, J. S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.5125-04.2005 · Cited by 164 · see citing works
Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake
Levenson, J. M., Weeber, E. J., Selcher, J. C., Kategaya, L. S., Sweatt, J. D., & Eskin, A. (2002) · Nature Neuroscience · doi:10.1038/nn791 · Cited by 150 · see citing works
Kunze, A., Congreso, M. R., Hartmann, C. J., Wallraff, A., Hüttmann, K., Bedner, P., Requardt, R. P., Seifert, G., Redecker, C., Willecke, K., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813160106 · Cited by 143 · see citing works
Poolos, N. P., Mauk, M. D., & Kocsis, J. D. (1987) · Journal of Neurophysiology · doi:10.1152/jn.1987.58.2.404 · Cited by 140 · see citing works
Substrate Turnover by Transporters Curtails Synaptic Glutamate Transients
Mennerick, S. J., Shen, W., Xu, W., Benz, A. M., Tanaka, K., Shimamoto, K., Isenberg, K. E., Krause, J. E., & Zorumski, C. F. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09242.1999 · Cited by 104 · see citing works
Mennerick, S. J., & Zorumski, C. F. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-04-03178.1995 · Cited by 91 · see citing works
Tsukada, S., Iino, M., Takayasu, Y., Shimamoto, K., & Ozawa, S. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2004.11.006 · Cited by 86 · see citing works
Hippocampal excitability and changes in extracellular potassium
Hablitz, J. J., & Lundervold, A. (1981) · Experimental Neurology · doi:10.1016/0014-4886(81)90099-6 · Cited by 81 · see citing works
The role of glial membrane ion channels in seizures and epileptogenesis
D’Ambrosio, R. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.05.004 · Cited by 75 · see citing works
Modulation of Glutamatergic Transmission by Bergmann Glial Cells in Rat Cerebellum In Situ
Bordey, A., & Sontheimer, H. W. (2003) · Journal of Neurophysiology · doi:10.1152/jn.00904.2002 · Cited by 45 · see citing works
Glucose transporter proteins in brain: Delivery of glucose to neurons and glia
Vannucci, S. J., Maher, F., & Simpson, I. A. (1997) · Glia · doi:10.1002/(sici)1098-1136(199709)21:1
Colombo (1999) · doi:10.1002/(sici)1098-1136(19990101)25:1
Flagged first, then by citations
Research works printed but not linked: 1
- [26]Giaume C, Tabernero A, Medina JM. Metabolic trafficking through astrocytic gap junctions. Glia. 1997;21:114–123. [PubMed] [Google Scholar]
Cited by
Sorted by citations
Glial responses to implanted electrodes in the brain
Salatino, J. W., Ludwig, K. A., Kozai, T. D. Y., & Purcell, E. K. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-017-0154-1 · Cited by 642 · see citing works
Hermann, D. M., & Chopp, M. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70039-x · Cited by 333 · see citing works
Beyond the GFAP-Astrocyte Protein Markers in the Brain
Jurga, A. M., Paleczna, M., Kadluczka, J., & Kuter, K. Z. (2021) · Biomolecules · doi:10.3390/biom11091361 · Cited by 319 · see citing works
Emerging role for astroglial networks in information processing: from synapse to behavior
Pannasch, U., & Rouach, N. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.04.004 · Cited by 251 · see citing works
Self-citationDeletion of Astroglial Connexins Weakens the Blood–Brain Barrier
Ezan, P., André, P., Cisternino, S., Saubaméa, B., Boulay, A.-C., Doutremer, S., Thomas, M.-A., Quenech'du, N., Giaume, C., & Cohen-Salmon, M. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.45 · Cited by 223 · see citing works
Self-citationSchiweck, J., Eickholt, B. J., & Murk, K. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00261 · Cited by 223 · see citing works
Stress gates an astrocytic energy reservoir to impair synaptic plasticity
Murphy-Royal, C., Johnston, A. D., Boyce, A. K. J., Diaz-Castro, B., Institoris, A., Peringod, G., Zhang, O., Stout, R. F., Spray, D. C., Thompson, R. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15778-9 · Cited by 158 · see citing works
Cell adhesion and matricellular support by astrocytes of the tripartite synapse
Hillen, A. E. J., Burbach, J. P. H., & Hol, E. M. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.02.002 · Cited by 108 · see citing works
Astroglial networks promote neuronal coordination
Chever, O., Dossi, E., Pannasch, U., Derangeon, M., & Rouach, N. (2016) · Science Signaling · doi:10.1126/scisignal.aad3066 · Cited by 107 · see citing works
Self-citationDeshpande, T., Li, T., Herde, M. K., Becker, A., Vatter, H., Schwarz, M. K., Henneberger, C., Steinhäuser, C., & Bedner, P. (2017) · Glia · doi:10.1002/glia.23196 · Cited by 87 · see citing works
Morioka, N., Suekama, K., Zhang, F. F., Kajitani, N., Hisaoka‐Nakashima, K., Takebayashi, M., & Nakata, Y. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12614 · Cited by 73 · see citing works
Immune Quiescence of the Brain Is Set by Astroglial Connexin 43
Boulay, A.-C., Mazeraud, A., Cisternino, S., Saubaméa, B., Mailly, P., Jourdren, L., Blugeon, C., Mignon, V., Smirnova, M., Cavallo, A., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2575-14.2015 · Cited by 69 · see citing works
Self-citationLutz, S. E., Raine, C. S., & Brosnan, C. F. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.01.007 · Cited by 30 · see citing works
- Authors
- Pannasch, U., Vargová, L., Reingruber, J., Ezan, P., Holcman, D., Giaume, C., Syková, E., & Rouach, N.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Department of Neuroscience and Center for Cell therapy and Tissue Repair, Charles University, Second Faculty of Medicine, 150 06 Prague, Czech Republic;
- Czech Academy of Sciences (CZ)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-05-02
- Volume
- 108
- Issue
- 20
- Pages
- 8467-8472
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3100942
- OpenAlex
- W2158211937
- Cited by
- 383
- References
- 34
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 23 · 2023: 22 · 2022: 17 · 2021: 28 · 2020: 30 · 2019: 24 · 2018: 31 · 2017: 23 · 2016: 22 · 2015: 26 · 2014: 31 · 2013: 31 · 2012: 38
- FWCI
- 13.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ASEP (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- astrocytes, connexin 30, connexin 43, gap junctions, synaptic transmission, synaptic plasticity, hippocampus, CA1 pyramidal neurons, glutamate clearance, potassium clearance, extracellular space volume, release probability, neuronal excitability, synaptogenesis
- MeSH terms
- Connexin 30, Animals, Astrocytes, Hippocampus, Nerve Net, Synaptic Transmission, Neuronal Plasticity, Potassium, Synapses, Gap Junctions, Connexins, Connexin 43, Glutamic Acid, Mice
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review