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Synaptic Efficacy Enhanced by Glial Cells in Vitro
Abstract
In the developing nervous system, glial cells guide axons to their target areas, but it is unknown whether they help neurons to establish functional synaptic connections. The role of glial cells in synapse formation and function was studied in cultures of purified neurons from the rat central nervous system. In glia-free cultures, retinal ganglion cells formed synapses with normal ultrastructure but displayed little spontaneous synaptic activity and high failure rates in evoked synaptic transmission. In cocultures with neuroglia, the frequency and amplitude of spontaneous postsynaptic currents were potentiated by 70-fold and 5-fold, respectively, and fewer transmission failures occurred. Glial cells increased the action potential–independent quantal release by 12-fold without affecting neuronal survival. Thus, developing neurons in culture form inefficient synapses that require glial signals to become fully functional.
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Araque, A., Parpura, V., Sanzgiri, R. P., & Haydon, P. G. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01349-6 · Cited by 2,529
The induction of pain: an integrative review
Millan, M. J. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00048-3 · Cited by 1,774
Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis
Christopherson, K. S., Ullian, E. M., Stokes, C. C. A., Mullowney, C. E., Hell, J. W., Agah, A., Lawler, J., Mosher, D. F., Bornstein, P., & Barres, B. A. (2005) · Cell · doi:10.1016/j.cell.2004.12.020 · Cited by 1,688
Self-citationCNS synaptogenesis promoted by glia-derived cholesterol
Mauch, D. H., Nägler, K., Schumacher, S., Göritz, C., Müller, E.-C., Otto, A., & Pfrieger, F. W. (2001) · Science · doi:10.1126/science.294.5545.1354 · Cited by 1,711
Self-citationVerkhratsky, A., & Nedergaard, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00042.2016 · Cited by 1,678
Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
Paşca, A. M., Sloan, S. A., Clarke, L. E., Tian, Y., Makinson, C. D., Huber, N., Kim, C. H., Park, J.-Y., O'Rourke, N. A., Nguyen, K. D., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3415 · Cited by 1,609
Self-citationDEVELOPMENT OF THE VERTEBRATE NEUROMUSCULAR JUNCTION
Sanes, J. R., & Lichtman, J. W. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.389 · Cited by 1,532
The Mystery and Magic of Glia: A Perspective on Their Roles in Health and Disease
Barres, B. A. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.013 · Cited by 1,352
Self-citationControl of Synapse Number by Glia
Ullian, E. M., Sapperstein, S. K., Christopherson, K. S., & Barres, B. A. (2001) · Science · doi:10.1126/science.291.5504.657 · Cited by 1,380
Self-citationControl of Synaptic Strength by Glial TNFα
Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., & Malenka, R. C. (2002) · Science · doi:10.1126/science.1067859 · Cited by 1,344
New roles for astrocytes: redefining the functional architecture of the brain.
Nedergaard, M., Ransom, B., & Goldman, S. A. (2003) · Trends in Neurosciences · doi:10.1016/j.tins.2003.08.008 · Cited by 1,334
Cell Biology of Astrocyte-Synapse Interactions
Allen, N. J., & Eroglu, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.056 · Cited by 1,098
Astrocyte Crosstalk in CNS Inflammation
Linnerbauer, M., Wheeler, M. A., & Quintana, F. J. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.012 · Cited by 989
Emerging roles of astrocytes in neural circuit development
Clarke, L. E., & Barres, B. A. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3484 · Cited by 975
Self-citationAstrocytes Control Synapse Formation, Function, and Elimination
Chung, W.-S., Allen, N. J., & Eroglu, C. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020370 · Cited by 839
Regulation of synaptic connectivity by glia.
Eroglu, C., & Barres, B. A. (2010) · Nature · doi:10.1038/nature09612 · Cited by 813
“Under these conditions, RGCs show little spontaneous synapse activity and form few synapses, whereas RGCs cultured in the presence of a feeding layer of astrocytes or astrocyte-conditioned medium show about tenfold more excitatory synapse activity and a fivefold to sevenfold increase in the number of synapse”
BackgroundSelf-citationSulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo
Nimmerjahn, A., Kirchhoff, F., Kerr, J. N. D., & Helmchen, F. (2004) · Nature Methods · doi:10.1038/nmeth706 · Cited by 784
Cotter, D., Mackay, D., Landau, S., Kerwin, R., & Everall, I. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.6.545 · Cited by 766
Cholesterol metabolism and homeostasis in the brain
Zhang, J., & Liu, Q. (2015) · Protein & Cell · doi:10.1007/s13238-014-0131-3 · Cited by 686
Astrocytes and disease: a neurodevelopmental perspective
Molofsky, A. V., Krenick, R., Ullian, E., Tsai, H.-H., Deneen, B., Richardson, W. D., Barres, B. A., & Rowitch, D. H. (2012) · Genes & Development · doi:10.1101/gad.188326.112 · Cited by 682
Self-citationAstrocyte Pathology in Major Depressive Disorder: Insights from Human Postmortem Brain Tissue
Rajkowska, G., & Stockmeier, C. (2013) · Current Drug Targets · doi:10.2174/13894501113149990156 · Cited by 603
Reelin, lipoprotein receptors and synaptic plasticity
Herz, J., & Chen, Y. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn2009 · Cited by 524
Depolarization and cAMP Elevation Rapidly Recruit TrkB to the Plasma Membrane of CNS Neurons
Meyer-Franke, A., Wilkinson, G. A., Kruttgen, A., Hu, M., Munro, E., Hanson, M. G., Reichardt, L. F., & Barres, B. A. (1998) · Neuron · doi:10.1016/s0896-6273(00)80586-3 · Cited by 516
Self-citationThe Indispensable Roles of Microglia and Astrocytes during Brain Development
Reemst, K., Noctor, S. C., Lucassen, P. J., & Hol, E. M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00566 · Cited by 516
Morales, I., Guzmán-MartÃnez, L., Cerda-Troncoso, C., FarÃas, G. A., & Maccioni, R. B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00112 · Cited by 490
MECHANISMS OF VERTEBRATE SYNAPTOGENESIS
Waites, C. L., Craig, A. M., & Garner, C. C. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144336 · Cited by 483
Glial cell abnormalities in major psychiatric disorders: the evidence and implications
Cotter, D. R., Pariante, C. M., & Everall, I. P. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00527-5 · Cited by 465
A neuron–glia signalling network in the active brain
Bezzi, P., & Volterra, A. (2001) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00223-3 · Cited by 446
Cotrina, M. L., Lin, J. H.-C., López-Garcı́a, J. C., Naus, C. C. G., & Nedergaard, M. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-08-02835.2000 · Cited by 388
Blasko, I., Stampfer‐Kountchev, M., Robatscher, P., Veerhuis, R., Eikelenboom, P., & Grubeck‐Loebenstein, B. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00101.x · Cited by 374
Uhlmann, E. J., Wong, M., Baldwin, R. L., Bajenaru, M. L., Onda, H., Kwiatkowski, D. J., Yamada, K., & Gutmann, D. H. (2002) · Annals of Neurology · doi:10.1002/ana.10283 · Cited by 372
Dynamic Aspects of CNS Synapse Formation
McAllister, A. K. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112830 · Cited by 368
Astrocyte regulation of synaptic behavior
Allen, N. J. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100913-013053 · Cited by 343
Hochstim, C., Deneen, B., Lukaszewicz, A., Zhou, Q., & Anderson, D. J. (2008) · Cell · doi:10.1016/j.cell.2008.02.046 · Cited by 331
Multiple mechanisms mediate cholesterol-induced synaptogenesis in a CNS neuron
Goritz, C., Mauch, D. H., & Pfrieger, F. W. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.02.006 · Cited by 330
Self-citationRole of cholesterol in synapse formation and function
Pfrieger, F. W. (2003) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(03)00024-5 · Cited by 325
Self-citationJohnson, M. A., Weick, J. P., Pearce, R. A., & Zhang, S.-C. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4562-06.2007 · Cited by 318
Outsourcing in the brain: Do neurons depend on cholesterol delivery by astrocytes?
Pfrieger, F. W. (2003) · BioEssays · doi:10.1002/bies.10195 · Cited by 308
Self-citationSynaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes
Sultan, S., Li, L., Moss, J., Petrelli, F., Cassé, F., Gebara, E., Lopatar, J., Pfrieger, F. W., Bezzi, P., Bischofberger, J., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.037 · Cited by 284
Self-citationGlial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse
Lacagnina, M. J., Rivera, P. D., & Bilbo, S. D. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.121 · Cited by 271
Synaptic Changes in Alzheimer's Disease
Gylys, K. H., Fein, J. A., Yang, F., Wiley, D. J., Miller, C. A., & Cole, G. M. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63436-0 · Cited by 253
Astrocyte-immune cell interactions in physiology and pathology
Han, R. T., Kim, R. D., Molofsky, A. V., & Liddelow, S. A. (2021) · Immunity · doi:10.1016/j.immuni.2021.01.013 · Cited by 223
Astrocytes locally translate transcripts in their peripheral processes
Sakers, K., Lake, A. M., Khazanchi, R., Ouwenga, R., Vasek, M. J., Dani, A., & Dougherty, J. D. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617782114 · Cited by 202
Faissner, A., Pyka, M., Geissler, M., Sobik, T., Frischknecht, R., Gundelfinger, E. D., & Seidenbecher, C. (2010) · Brain Research Reviews · doi:10.1016/j.brainresrev.2010.01.001 · Cited by 207
Neuroplasticity in Alzheimer's disease
Teter, B., & Ashford, J. W. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10441 · Cited by 170
Astrocytes prevent abnormal neuronal development in the fragile X mouse.
Jacobs, S., & Doering, L. C. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5027-09.2010 · Cited by 170
Ballistic labeling and dynamic imaging of astrocytes in organotypic hippocampal slice cultures.
Benediktsson, A. M., Schachtele, S. J., Green, S. H., & Dailey, M. E. (2005) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2004.05.013 · Cited by 166
Astrocytic ApoE reprograms neuronal cholesterol metabolism and histone-acetylation-mediated memory
Li, X., Zhang, J., Li, D., He, C., He, K., Xue, T., Wan, L., Zhang, C., & Liu, Q. (2021) · Neuron · doi:10.1016/j.neuron.2021.01.005 · Cited by 165
Formation and function of apolipoprotein E-containing lipoproteins in the nervous system
Vance, J. E., & Hayashi, H. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.02.007 · Cited by 155
Astrocyte–neuron interactions in neurological disorders
Ricci, G., Volpi, L., Pasquali, L., Petrozzi, L., & Siciliano, G. (2009) · Journal of Biological Physics · doi:10.1007/s10867-009-9157-9 · Cited by 155
Huang, Y.-W. A., Zhou, B., Nabet, A. M., Wernig, M., & Südhof, T. C. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.2994-18.2019 · Cited by 152
ATP-binding cassette transporter A1: From metabolism to neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.007 · Cited by 144
“Previous studies have reported that cholesterol is needed for neurites outgrowth and repair, and synaptic vesicle formation and regeneration (Pfrieger and Barres, 1997).”
Interlaminar astroglia of the cerebral cortex: a marker of the primate brain
Colombo, J. A., & Reisin, H. D. (2004) · Brain Research · doi:10.1016/j.brainres.2004.02.003 · Cited by 132
Role of glial cells in the formation and maintenance of synapses
Pfrieger, F. W. (2010) · Brain Research Reviews · doi:10.1016/j.brainresrev.2009.11.002 · Cited by 124
Self-citationGarcia, O., Torres, M., Helguera, P., Coskun, P., & Busciglio, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014200 · Cited by 122
The cell biology of APOE in the brain
Windham, I. A., & Cohen, S. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.09.004 · Cited by 103
The role of ATP-binding cassette transporter A1 in Alzheimer's disease and neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.02.010 · Cited by 102
APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size
Windham, I. A., Powers, A. E., Ragusa, J. V., Wallace, E. D., Zanellati, M. C., Williams, V. H., Wagner, C. H., White, K. K., & Cohen, S. (2024) · Journal of Cell Biology · doi:10.1083/jcb.202305003 · Cited by 96
Role of glia-derived cholesterol in synaptogenesis: new revelations in the synapse–glia affair
Göritz, C., Mauch, D. H., Nägler, K., & Pfrieger, F. W. (2002) · Journal of Physiology-Paris · doi:10.1016/s0928-4257(02)00014-1 · Cited by 88
Self-citationCaldwell, A. L. M., Sancho, L., Deng, J., Bosworth, A., Miglietta, A., Diedrich, J. K., Shokhirev, M. N., & Allen, N. J. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01150-1 · Cited by 86
Cheng, C., Lau, S. K. M., & Doering, L. C. (2016) · Molecular Brain · doi:10.1186/s13041-016-0256-9 · Cited by 84
Sonnay, S., Gruetter, R., & Duarte, J. M. N. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00288 · Cited by 74
Falcone, C., Penna, E., Hong, T., Tarantal, A. F., Hof, P. R., Hopkins, W. D., Sherwood, C. C., Noctor, S. C., & Martínez-Cerdeño, V. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhaa231 · Cited by 72
Long-term culture of astrocytes attenuates the readily releasable pool of synaptic vesicles
Kawano, H., Katsurabayashi, S., Kakazu, Y., Yamashita, Y., Kubo, N., Kubo, M., Okuda, H., Takasaki, K., Kubota, K., Mishima, K., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048034 · Cited by 68
Bosch, C., Masachs, N., Exposito-Alonso, D., Martínez, A., Teixeira, C. M., Fernaud, I., Pujadas, L., Ulloa, F., Comella, J. X., DeFelipe, J., et al. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw216 · Cited by 70
Yang, Q., Feng, B., Zhang, K., Guo, Y.-Y., Liu, S.-B., Wu, Y.-M., Li, X.-Q., & Zhao, M.-G. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003172 · Cited by 59
Krzisch, M., Temprana, S. G., Mongiat, L. A., Armida, J., Schmutz, V., Virtanen, M. A., Kocher-Braissant, J., Kraftsik, R., Vutskits, L., Conzelmann, K.-K., et al. (2015) · Brain Structure and Function · doi:10.1007/s00429-014-0768-y · Cited by 57
Redefining varicose projection astrocytes in primates.
Falcone, C., McBride, E. L., Hopkins, W. D., Hof, P. R., Manger, P. R., Sherwood, C. C., Noctor, S. C., & Martínez‐Cerdeño, V. (2022) · Glia · doi:10.1002/glia.24093 · Cited by 56
Back and forth in time: Directing age in iPSC-derived lineages
Cornacchia, D., & Studer, L. (2017) · Brain Research · doi:10.1016/j.brainres.2015.11.013 · Cited by 56
VanderWall, K. B., Vij, R., Ohlemacher, S. K., Sridhar, A., Fligor, C. M., Feder, E. M., Edler, M. C., Baucum, A. J., Cummins, T. R., & Meyer, J. S. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.12.010 · Cited by 46
ABCG1 and ABCG4 Suppress γ-Secretase Activity and Amyloid β Production
Sano, O., Tsujita, M., Shimizu, Y., Kato, R., Kobayashi, A., Kioka, N., Remaley, A. T., Michikawa, M., Ueda, K., & Matsuo, M. (2016) · PLOS ONE · doi:10.1371/journal.pone.0155400 · Cited by 47
Satellite Glial Cells: Morphology, functional heterogeneity, and role in pain
Andreeva, D., Murashova, L., Burzak, N., & Dyachuk, V. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.1019449 · Cited by 38
Considerations on the astroglial architecture and the columnar organization of the cerebral cortex.
Reisin, H. D., & Colombo, J. A. (2002) · Cellular and Molecular Neurobiology · doi:10.1023/a:1021892521180 · Cited by 31
Astrocytes and developmental plasticity in fragile X.
Cheng, C., Sourial, M., & Doering, L. C. (2012) · Neural Plasticity · doi:10.1155/2012/197491 · Cited by 28
Subtype diversification and synaptic specificity of stem cell-derived spinal interneurons
Hoang, P. T., Chalif, J. I., Bikoff, J. B., Jessell, T. M., Mentis, G. Z., & Wichterle, H. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.016 · Cited by 25
Glial-toxin-mediated disruption of spinal cord locomotor network function and its modulation by 5-HT
Baudoux, S., & Parker, D. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.03.034 · Cited by 14
Evolution of Astrocyte-Neuron Interactions Across Species
Ciani, C., Ayub, M., & Falcone, C. (2024) · Advances in Neurobiology · doi:10.1007/978-3-031-64839-7_1 · Cited by 7
Metadata
- Authors
- Pfrieger, F. W., & Barres, B. A.
- Venue
- Science
- Published
- 1997-09-12
- Volume
- 277
- Issue
- 5332
- Pages
- 1684-1687
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1996603253
- Cited by
- 793
- References
- 0
- FWCI
- 8.61
- Type
- journal article
- Language
- en
- Open access
- closed
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