Miniature synaptic events maintain dendritic spines via AMPA receptor activation
Abstract
We investigated the influence of synaptically released glutamate on postsynaptic structure by comparing the effects of deafferentation, receptor antagonists and blockers of glutamate release in hippocampal slice cultures. CA1 pyramidal cell spine density and length decreased after transection of Schaffer collaterals and after application of AMPA receptor antagonists or botulinum toxin to unlesioned cultures. Loss of spines induced by lesion or by botulinum toxin was prevented by simultaneous AMPA application. Tetrodotoxin did not affect spine density. Synaptically released glutamate thus exerts a trophic effect on spines by acting at AMPA receptors. We conclude that AMPA receptor activation by spontaneous vesicular glutamate release is sufficient to maintain dendritic spines.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Blocking AMPA-R activity with NBQX significantly reduced spine density.
“Blocking AMPA-R activity with NBQX significantly reduced spine density (23)”
From AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade (2009) · cites this paper as [23]
Neurotransmitters including norepinephrine, serotonin and glutamate, as well as stress-induced release of neuropeptides and steroids, can influence synapse number and function.
“Neurotransmitters, including norepinephrine,76, 77, 78 serotonin79, 80, 81 and glutamate,82,83 as well as stress-induced release of neuropeptides26,34,84,85 and steroids,86, 87, 88 can influence synapse number and function.”
From Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress (2014) · cites this paper as [83]
Cites
Reactivation of hippocampal ensemble memories during sleep
Wilson, M. A., & McNaughton, B. L. (1994) · Science · doi:10.1126/science.8036517 · Cited by 3,118 · see citing works
Ca2 + Permeability of KA-AMPA—Gated Glutamate Receptor Channels Depends on Subunit Composition
Hollmann, M., Hartley, M., & Heinemann, S. F. (1991) · Science · doi:10.1126/science.1709304 · Cited by 1,450 · see citing works
Liao, D., Hessler, N. A., & Malinow, R. (1995) · Nature · doi:10.1038/375400a0 · Cited by 1,365 · see citing works
Banker, G. A., & Goslin, K. (1998) · Cited by 1,290 · 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
Harris, K., & Stevens, J. (1989) · The Journal of Neuroscience · doi:10.1523/jneurosci.09-08-02982.1989 · Cited by 1,073 · see citing works
Harris, K. M., Jensen, F. E., & Tsao, B. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-07-02685.1992 · Cited by 990 · see citing works
Rapid Actin-Based Plasticity in Dendritic Spines
Fischer, M., Kaech, S., Knutti, D., & Matus, A. (1998) · Neuron · doi:10.1016/s0896-6273(00)80467-5 · Cited by 905 · see citing works
NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms
Malenka, R. C., & Nicoll, R. A. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90197-t · Cited by 904 · see citing works
Evidence for a Role of Dendritic Filopodia in Synaptogenesis and Spine Formation
Ziv, N. E., & Smith, S. J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80283-4 · Cited by 863 · see citing works
Synaptogenesis Via Dendritic Filopodia in Developing Hippocampal Area CA1
Fiala, J. C., Feinberg, M., Popov, V., & Harris, K. M. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-21-08900.1998 · Cited by 758 · see citing works
The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines
Peters, A., & Kaiserman‐Abramof, I. R. (1970) · American Journal of Anatomy · doi:10.1002/aja.1001270402 · Cited by 740 · see citing works
Woolley, C. S., & McEwen, B. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-12-07680.1994 · Cited by 679 · see citing works
Moser, M., Trommald, M., & Andersen, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.26.12673 · Cited by 615 · see citing works
Control of ACh sensitivity by muscle activity in the rat
Lømo, T., & Rosenthal, J. (1972) · The Journal of Physiology · doi:10.1113/jphysiol.1972.sp009764 · Cited by 533 · see citing works
The small pyramidal neuron of the rat cerebral cortex: The synapses upon dendritic spines
Peters, A., & Kaiserman-Abramof, I. R. (1969) · Zeitschrift f�r Zellforschung und Mikroskopische Anatomie · doi:10.1007/bf00344370 · Cited by 441 · see citing works
Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons
Papa, M., Bundman, M. C., Greenberger, V., & Segal, M. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-01-00001.1995 · Cited by 330 · see citing works
Contributions of dendritic spines and perforated synapses to synaptic plasticity
Calverley, R. K. S., & Jones, D. G. (1990) · Brain Research Reviews · doi:10.1016/0165-0173(90)90002-6 · Cited by 277 · see citing works
Jonas, P., & Sakmann, B. (1992) · The Journal of Physiology · doi:10.1113/jphysiol.1992.sp019294 · Cited by 271 · see citing works
Quantal analysis and synaptic anatomy--integrating two views of hippocampal plasticity.
Lisman, J., & Harris, K. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90122-3 · Cited by 271 · see citing works
Westrum, L. E., & Blackstad, T. W. (1962) · The Journal of Comparative Neurology · doi:10.1002/cne.901190303 · Cited by 237 · see citing works
Modulatory Role of Drebrin on the Cytoskeleton within Dendritic Spines in the Rat Cerebral Cortex
Hayashi, K., Ishikawa, R., Ye, L., He, X., Takata, K., Kohama, K., & Shirao, T. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-22-07161.1996 · Cited by 217 · see citing works
Spine Loss and Regrowth in Hippocampus following Deafferentation
Parnavelas, J. G., LYNCH, G. S., Brecha, N. C., Cotman, C. W., & Globus, A. (1974) · Nature · doi:10.1038/248071a0 · Cited by 198 · see citing works
Stability in Synapse Number and Size at 2 Hr after Long-Term Potentiation in Hippocampal Area CA1
Sorra, K. E., & Harris, K. M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-02-00658.1998 · Cited by 181 · see citing works
Edwards, F. A. (1995) · Physiological Reviews · doi:10.1152/physrev.1995.75.4.759 · Cited by 179 · see citing works
McKinney, R. A., Debanne, D., Gähwiler, B. H., & Thompson, S. M. (1997) · Nature Medicine · doi:10.1038/nm0997-990 · Cited by 157 · see citing works
Self-citationChanges in the structure of synapses associated with learning
Horn, G., Bradley, P. M., & Bj, M. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-12-03161.1985 · Cited by 155 · see citing works
AMPA receptor-mediated regulation of a Gi-protein in cortical neurons
Wang, Y., Small, D. L., Stanimirovic, D. B., et al. (1997) · Nature · doi:10.1038/39062 · Cited by 153 · see citing works
Capogna, M., McKinney, R. A., O'Connor, V. M., Gähwiler, B. H., & Thompson, S. M. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-19-07190.1997 · Cited by 149 · see citing works
Self-citationWickens, J. R. (1988) · Progress in Neurobiology · doi:10.1016/0301-0082(88)90013-5 · Cited by 112 · see citing works
Trommald, M., Jensen, V., & Andersen, P. N. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903530208 · Cited by 106 · see citing works
Goldowitz, D., Scheff, S. W., & Cotman, C. W. (1979) · Brain Research · doi:10.1016/0006-8993(79)90962-4 · Cited by 62 · see citing works
Cooper, M. W., & Smith, S. J. (1992) · Journal of Neurobiology · doi:10.1002/neu.480230704 · Cited by 58 · see citing works
Gerfin-Moser, A., Grogg, F., Rietschin, L., Thompson, S. M., & Streit, P. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00130-b · Cited by 36 · see citing works
Quantification of dendritic spine populations using image analysis and a tilting disector
Rusakov, D. A., & Stewart, M. G. (1995) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(94)00215-3 · Cited by 35 · see citing works
Quantal Neurotransmitter Release and the Clostridial Neurotoxins’ Targets
Poulain, B., Molgó, J., & Thesleff, S. (1995) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-85173-5_11 · Cited by 29 · see citing works
Developmental neurotrophin expression in slice cultures of rat hippocampus
Förster, E., Otten, U., & Frotscher, M. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90711-s · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Excitatory actions of gaba during development: the nature of the nurture
Ben-Ari, Y. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn920 · Cited by 2,448 · see citing works
PSD-95 Involvement in Maturation of Excitatory Synapses
El-Husseini, A. E.-D., Schnell, E., Chetkovich, D. M., Nicoll, R. A., & Bredt, D. S. (2000) · Science · doi:10.1126/science.290.5495.1364 · Cited by 1,303 · see citing works
Structure and function of dendritic spines
Nimchinsky, E. A., Sabatini, B. L., & Svoboda, K. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.081501.160008 · Cited by 1,208 · see citing works
Hoover, B. R., Reed, M. N., Su, J., Penrod, R. D., Kotilinek, L. A., Grant, M. K., Pitstick, R., Carlson, G. A., Lanier, L. M., Yuan, L.-L., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.030 · Cited by 1,118 · see citing works
Dentritic spines : structure, dynamics and regulation
Hering, H., & Sheng, M. (2001) · Nature Reviews Neuroscience · doi:10.1038/35104061 · Cited by 961 · see citing works
Origin of Slow Cortical Oscillations in Deafferented Cortical Slabs
Timofeev, I. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.12.1185 · Cited by 710 · see citing works
Inactivity produces increases in neurotransmitter release and synapse size
Murthy, V. N., Schikorski, T., Stevens, C. F., & Zhu, Y. (2001) · Neuron · doi:10.1016/s0896-6273(01)00500-1 · Cited by 612 · see citing works
Dendritic spine pathology in schizophrenia
Glausier, J. R., & Lewis, D. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.04.044 · Cited by 581 · see citing works
Local Ca2+ detection and modulation of synaptic release by astrocytes
Di Castro, M. A., Chuquet, J., Liaudet, N., Bhaukaurally, K., Santello, M., Bouvier, D., Tiret, P., & Volterra, A. (2011) · Nature Neuroscience · doi:10.1038/nn.2929 · Cited by 529 · see citing works
Dendritic structural plasticity and neuropsychiatric disease
Forrest, M. P., Parnell, E., & Penzes, P. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.16 · Cited by 464 · see citing works
Shors, T. J., Chua, C., & Falduto, J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-16-06292.2001 · Cited by 496 · see citing works
The mechanisms and functions of spontaneous neurotransmitter release
Kavalali, E. T. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3875 · Cited by 486 · see citing works
Developmental regulation of spine motility in the mammalian central nervous system
Dunaevsky, A., Tashiro, A., Majewska, A., Mason, C., & Yuste, R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.23.13438 · Cited by 412 · see citing works
Miller, O. H., Yang, L., Wang, C.-C., Hargroder, E. A., Zhang, Y., Delpire, E., & Hall, B. J. (2014) · eLife · doi:10.7554/elife.03581 · Cited by 358 · see citing works
Bonhoeffer, T., & Yuste, R. (2002) · Neuron · doi:10.1016/s0896-6273(02)00906-6 · Cited by 337 · see citing works
The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies
Hu, W., MacDonald, M. L., Elswick, D. E., & Sweet, R. A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12547 · Cited by 286 · see citing works
Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia
Sweet, R. A., Henteleff, R. A., Zhang, W., Sampson, A. R., & Lewis, D. A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.67 · Cited by 290 · see citing works
Shank Expression Is Sufficient to Induce Functional Dendritic Spine Synapses in Aspiny Neurons
Roussignol, G., Ango, F., Romorini, S., Tu, J. C., Sala, C., Worley, P. F., Bockaert, J., & Fagni, L. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4354-04.2005 · Cited by 293 · see citing works
Dendritic Spine Dynamics Are Regulated by Monocular Deprivation and Extracellular Matrix Degradation
Oray, S., Majewska, A., & Sur, M. (2004) · Neuron · doi:10.1016/j.neuron.2004.12.001 · Cited by 296 · see citing works
Sala, C., Futai, K., Yamamoto, K., Worley, P. F., Hayashi, Y., & Sheng, M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06327.2003 · Cited by 288 · see citing works
Hassert, D. L., Miyashita, T., & Williams, C. L. (2004) · Behavioral Neuroscience · doi:10.1037/0735-7044.118.1.79 · Cited by 284 · see citing works
Sutton, M. A., Taylor, A. M., Ito, H. T., Pham, A., & Schuman, E. M. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.030 · Cited by 274 · see citing works
Miller, O. H., Moran, J. T., & Hall, B. J. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.07.028 · Cited by 200 · see citing works
Iadarola, N. D., Niciu, M. J., Richards, E. M., Vande Voort, J. L., Ballard, E. D., Lundin, N. B., Nugent, A. C., Machado-Vieira, R., & Zarate, C. A. (2015) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622315579059 · Cited by 201 · see citing works
Otsu, Y., Shahrezaei, V., Li, B., Raymond, L. A., Delaney, K. R., & Murphy, T. H. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4452-03.2004 · Cited by 169 · see citing works
Chen, N., & Napoli, J. L. (2008) · The FASEB Journal · doi:10.1096/fj.07-8739com · Cited by 166 · see citing works
v-SNARE composition distinguishes synaptic vesicle pools
Hua, Z., Leal-Ortiz, S., Foss, S. M., Waites, C. L., Garner, C. C., Voglmaier, S. M., & Edwards, R. H. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.010 · Cited by 168 · see citing works
Glutamate induces the rapid formation of spine head protrusions in hippocampal slice cultures
Richards, D. A., Mateos, J. M., Hugel, S., de Paola, V., Caroni, P., Gähwiler, B. H., & McKinney, R. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501881102 · Cited by 161 · see citing works
Self-citationAMPA receptors as drug targets in neurological disease—advantages, caveats, and future outlook
Chang, P. K. ‐., Verbich, D., & McKinney, R. A. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08165.x · Cited by 155 · see citing works
Self-citationDifferential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels
Ermolyuk, Y. S., Alder, F. G., Surges, R., Pavlov, I. Y., Timofeeva, Y., Kullmann, D. M., & Volynski, K. E. (2013) · Nature Neuroscience · doi:10.1038/nn.3563 · Cited by 148 · see citing works
Antiepileptic drugs and the developing brain
Kaindl, A. M., Asimiadou, S., Manthey, D., Hagen, M. V. D., Turski, L., & Ikonomidou, C. (2006) · Cellular and Molecular Life Sciences CMLS · doi:10.1007/s00018-005-5348-0 · Cited by 121 · see citing works
Maras, P. M., Molet, J., Chen, Y., Rice, C., Ji, S. G., Solodkin, A., & Baram, T. Z. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.12 · Cited by 118 · see citing works
Remodeling of Hippocampal Synaptic Networks by a Brief Anoxia–Hypoglycemia
Jourdain, P., Nikonenko, I., Alberi, S., & Muller, D. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03108.2002 · Cited by 116 · see citing works
Approaches and Limitations in the Investigation of Synaptic Transmission and Plasticity
Glasgow, S. D., McPhedrain, R., Madranges, J. F., Kennedy, T. E., & Ruthazer, E. S. (2019) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2019.00020 · Cited by 100 · see citing works
Kang, M.-G., Guo, Y., & Huganir, R. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812861106 · Cited by 82 · see citing works
Measles Virus Spreads in Rat Hippocampal Neurons by Cell-to-Cell Contact and in a Polarized Fashion
Ehrengruber, M. U., Ehler, E., Billeter, M. A., & Naim, H. Y. (2002) · Journal of Virology · doi:10.1128/jvi.76.11.5720-5728.2002 · Cited by 73 · see citing works
Campbell, J. N., Register, D., & Churn, S. B. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2011.1761 · Cited by 70 · see citing works
Neurotransmitters and the Development of Neuronal Circuits
Ruediger, T., & Bolz, J. (2007) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-387-76715-4_8 · Cited by 62 · see citing works
Mateos, J. M., Lüthi, A., Savic, N., Stierli, B., Streit, P., Gähwiler, B. H., & McKinney, R. A. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2006.120550 · Cited by 53 · see citing works
Self-citationTwo distinct oscillatory states determined by the NMDA receptor in rat inferior olive
Placantonakis, D. G., & Welsh, J. P. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.t01-1-00123.x · Cited by 49 · see citing works
de Vasconcellos-Bittencourt, A. P. S., Vendite, D. A., Nassif, M., Crema, L. M., Frozza, R., Thomazi, A. P., Nieto, F. B., Wofchuk, S., Salbego, C., da Rocha, E. R., et al. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0404-7 · Cited by 36 · see citing works
- Authors
- McKinney, R. A., Capogna, M., Dürr, R., Gähwiler, B. H., & Thompson, A. S. M.
- Affiliations
- University of Zurich (CH)
- Aarhus University (DK)
- University of Maryland, Baltimore (US)
- Corresponding author
- McKinney, R. Anne
- Venue
- Nature Neuroscience
- Published
- 1999-01
- Volume
- 2
- Issue
- 1
- Pages
- 44-49
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- DOI
- 10.1038/4548
- OpenAlex
- W1534752637
- Cited by
- 523
- References
- 37
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 12 · 2022: 3 · 2021: 10 · 2020: 10 · 2019: 7 · 2018: 10 · 2017: 22 · 2016: 10 · 2015: 20 · 2014: 19 · 2013: 24 · 2012: 28
- FWCI
- 11.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dendritic spines, AMPA receptors, glutamate release, synaptic plasticity, CA1 pyramidal neurons, Schaffer collaterals, deafferentation, botulinum toxin, tetrodotoxin, spine density, spine length, hippocampus, vesicular glutamate release
- MeSH terms
- Afferent Pathways, Botulinum Toxins, Dendrites, Denervation, Hippocampus, Synapses, Tetrodotoxin, Receptors, AMPA, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Excitatory Amino Acid Antagonists, Glutamic Acid, In Vitro Techniques
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