Distinct structural and ionotropic roles of NMDA receptors in controlling spine and synapse stability
Abstract
NMDA-type glutamate receptors (NMDARs) play a central role in the rapid regulation of synaptic transmission, but their contribution to the long-term stabilization of glutamatergic synapses is unknown. We find that, in hippocampal pyramidal neurons in rat organotypic slices, pharmacological blockade of NMDARs does not affect synapse formation and dendritic spine growth but does increase the motility of spines. Physical loss of synaptic NMDARs induced by RNA interference against the NR1 subunit of the receptor also increases the motility of spines. Furthermore, knock-down of NMDARs, but not their pharmacological block, destabilizes spine structure and over time leads to loss of spines and excitatory synapses. Maintenance of normal spine density requires the coexpression of two specific splice isoforms of the NR1 subunit that contain the C-terminal C2 cassette. Thus, although ionotropic properties of NMDARs induce synaptic plasticity, it is the physical interactions of the C-tail of the receptor that mediate the long-term stabilization of synapses and spines.
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?
Unlike NR1 and NR2B, NR2A has so far not been linked to spine morphogenesis.
“but unlike NR1 and NR2B, this NMDAR subunit has so far not been linked to spine morphogenesis (Alvarez et al., 2007; Kim et al., 2005; Ultanir et al., 2007).”
From Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 (2010) · cites this paper as Alvarez et al., 2007
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
Rampon, C., Tang, Y.-P., Goodhouse, J., Shimizu, E., Kyin, M., & Tsien, J. Z. (2000) · Nature Neuroscience · doi:10.1038/72945 · Cited by 737 · see citing works
Competitive binding of α-actinin and calmodulin to the NMDA receptor
Wyszynski, M., Lin, J., Rao, A., Nigh, E., Beggs, A. H., Craig, A. M., & Sheng, M. (1997) · Nature · doi:10.1038/385439a0 · Cited by 596 · see citing works
Molecular determinants of NMDA receptor internalization
Roche, K. W., Standley, S., McCallum, J., Dune Ly, C., Ehlers, M. D., & Wenthold, R. J. (2001) · Nature Neuroscience · doi:10.1038/90498 · Cited by 550 · see citing works
Subunit-Specific NMDA Receptor Trafficking to Synapses
Barria, A., & Malinow, R. (2002) · Neuron · doi:10.1016/s0896-6273(02)00776-6 · Cited by 515 · see citing works
Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2
Tavazoie, S. F., Alvarez, V. A., Ridenour, D. A., Kwiatkowski, D. J., & Sabatini, B. L. (2005) · Nature Neuroscience · doi:10.1038/nn1566 · Cited by 497 · see citing works
Self-citationLong-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex
Zuo, Y., Yang, G., Kwon, E., & Gan, W.-B. (2005) · Nature · doi:10.1038/nature03715 · Cited by 436 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Nagerl UV, Eberhorn N, Cambridge SB, Bonhoeffer T (2004) Bidirectional activity-dependent morphological plasticity in hippocampal neurons. Neuron 44:759 -767.
Cited by
Sorted by citations
Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132
Edbauer, D., Neilson, J. R., Foster, K. A., Wang, C.-F., Seeburg, D. P., Batterton, M. N., Tada, T., Dolan, B. M., Sharp, P. A., & Sheng, M. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.005 · Cited by 735 · see citing works
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · 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
Bhatt, D. H., Zhang, S., & Gan, W.-B. (2009) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163140 · Cited by 380 · see citing works
Raven, F., Van der Zee, E. A., Meerlo, P., & Havekes, R. (2018) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2017.05.002 · Cited by 331 · see citing works
GABA Regulates Excitatory Synapse Formation in the Neocortex via NMDA Receptor Activation
Wang, D. D., & Kriegstein, A. R. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5599-07.2008 · Cited by 299 · see citing works
Stress and trauma: BDNF control of dendritic-spine formation and regression
Bennett, M. R., & Lagopoulos, J. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.10.005 · Cited by 199 · see citing works
Ampuero, E., Rubio, F. J., Falcon, R., Sandoval, M., Diaz-Veliz, G., Gonzalez, R. E., Earle, N., Dagnino-Subiabre, A., Aboitiz, F., Orrego, F., et al. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.04.035 · Cited by 132 · see citing works
Spatial and temporal boundaries of NMDA receptor hypofunction leading to schizophrenia
Nakazawa, K., Jeevakumar, V., & Nakao, K. (2017) · npj Schizophrenia · doi:10.1038/s41537-016-0003-3 · Cited by 110 · see citing works
Presynaptic Release Probability Is Increased in Hippocampal Neurons From ASIC1 Knockout Mice
Cho, J.-H., & Askwith, C. C. (2008) · Journal of Neurophysiology · doi:10.1152/jn.00940.2007 · Cited by 67 · see citing works
Arnold, P. D., MacMaster, F. P., Hanna, G. L., Richter, M. A., Sicard, T., Burroughs, E., Mirza, Y., Easter, P. C., Rose, M., Kennedy, J. L., et al. (2009) · Brain Imaging and Behavior · doi:10.1007/s11682-008-9050-3 · Cited by 46 · see citing works
Khalil, O. S., Forrest, C. M., Pisar, M., Smith, R. A., Darlington, L. G., & Stone, T. W. (2013) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923973.2013.828745 · Cited by 14 · see citing works
- Authors
- Alvarez, V. A., Ridenour, D. A., & Sabatini, B. L.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-07-11
- Volume
- 27
- Issue
- 28
- Pages
- 7365-7376
- ISSN
- 0270-6474
- 1529-2401
- Cited by
- 117
- References
- 6
- Language
- en
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
