Spine neck plasticity regulates compartmentalization of synapses
Abstract
Dendritic spines have been proposed to transform synaptic signals through chemical and electrical compartmentalization. However, the quantitative contribution of spine morphology to synapse compartmentalization and its dynamic regulation are still poorly understood. We used time-lapse super-resolution stimulated emission depletion (STED) imaging in combination with fluorescence recovery after photobleaching (FRAP) measurements, two-photon glutamate uncaging, electrophysiology and simulations to investigate the dynamic link between nanoscale anatomy and compartmentalization in live spines of CA1 neurons in mouse brain slices. We report a diversity of spine morphologies that argues against common categorization schemes and establish a close link between compartmentalization and spine morphology, wherein spine neck width is the most critical morphological parameter. We demonstrate that spine necks are plastic structures that become wider and shorter after long-term potentiation. These morphological changes are predicted to lead to a substantial drop in spine head excitatory postsynaptic potential (EPSP) while preserving overall biochemical compartmentalization.
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?
Two-photon glutamate uncaging experiments on single spines indicate that synapses that already express functional AMPARs can be further enhanced by inducing LTP.
“Furthermore, two-photon glutamate uncaging experiments on single spines indicate that synapses that already express functional AMPARs can be further enhanced by inducing LTP (246–248).”
From Synaptic memory and CaMKII (2023) · cites this paper as [248]
LTP is associated with a long-lasting increase in spine size, including a late increase in the size of the PSD and a slow increase in the size of the presynaptic bouton.
“LTP is associated with a long-lasting increase in spine size (247, 248), including a late increase in the size of the PSD (56, 213, 414, 415) and additionally a slow increase in the size of the presynaptic bouton (213, 414).”
From Synaptic memory and CaMKII (2023) · cites this paper as [248]
Parallel to the electrophysiological changes during LTP is an enlargement of the spine and a widening of the spine neck.
“Parallel to the electrophysiological changes during LTP is an enlargement of the spine and a widening of the spine neck (247, 248).”
From Synaptic memory and CaMKII (2023) · cites this paper as [248]
LTP-inducing stimuli cause rapid addition of AMPARs to classical dendritic spines.
“These synapses contain AMPARs, but LTP-inducing stimuli cause a rapid addition of AMPARs to the synapse (246–250).”
From Synaptic memory and CaMKII (2023) · cites this paper as [248]
The section “LTP leads to plasticity in spine head and neck geometry” (pp. 10–11) reports potentiated currents and changes in spine shape after LTP induction, but does not say that AMPARs were rapidly added to synapses. Searches for AMPAR insertion and rapid receptor addition found no passage addressing that mechanism in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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
Structural basis of long-term potentiation in single dendritic spines
Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. R., & Kasai, H. (2004) · Nature · doi:10.1038/nature02617 · Cited by 2,500 · see citing works
Experience-dependent structural synaptic plasticity in the mammalian brain
Holtmaat, A., & Svoboda, K. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2699 · Cited by 1,934 · see citing works
Matsuzaki, M., Ellis-Davies, G. C. R., Nemoto, T., Miyashita, Y., Iino, M., & Kasai, H. (2001) · Nature Neuroscience · doi:10.1038/nn736 · Cited by 1,563 · 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
Locally dynamic synaptic learning rules in pyramidal neuron dendrites
Harvey, C. D., & Svoboda, K. (2007) · Nature · doi:10.1038/nature06416 · Cited by 625 · see citing works
Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines
Tanaka, J.-I., Horiike, Y., Matsuzaki, M., Miyazaki, T., Ellis-Davies, G. C. R., & Kasai, H. (2008) · Science · doi:10.1126/science.1152864 · Cited by 615 · 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
Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study.
Nevian, T., Larkum, M. E., Polsky, A., & Schiller, J. (2007) · Nature Neuroscience · doi:10.1038/nn1826 · Cited by 406 · see citing works
Synaptic amplification by dendritic spines enhances input cooperativity
Harnett, M. T., Makara, J. K., Spruston, N., Kath, W. L., & Magee, J. C. (2012) · Nature · doi:10.1038/nature11554 · Cited by 288 · see citing works
Crick, F. (1982) · Trends in Neurosciences · doi:10.1016/0166-2236(82)90020-0 · Cited by 254 · see citing works
Lang, C., Barco, A., Zablow, L., Kandel, E. R., Siegelbaum, S. A., & Zakharenko, S. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407581101 · Cited by 245 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [7]7. Nägerl, U.V., Eberhorn, N., Cambridge, S.B. & Bonhoeffer, T. Bidirectional activity-dependent morphological plasticity in hippocampal neurons. Neuron 44 , 759-767 (2004).
Cited by
Sorted by citations
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
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
Biochemical Computation for Spine Structural Plasticity
Nishiyama, J., & Yasuda, R. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.043 · Cited by 199 · see citing works
Activity-dependent dendritic spine neck changes are correlated with synaptic strength
Araya, R., Vogels, T. P., & Yuste, R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321869111 · Cited by 197 · see citing works
Incontro, S., Díaz-Alonso, J., Iafrati, J., Vieira, M., Asensio, C. S., Sohal, V. S., Roche, K. W., Bender, K. J., & Nicoll, R. A. (2018) · Nature Communications · doi:10.1038/s41467-018-04439-7 · Cited by 171 · see citing works
Actin Out: Regulation of the Synaptic Cytoskeleton
Spence, E. F., & Soderling, S. H. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.655118 · Cited by 171 · see citing works
Early postnatal development of pyramidal neurons across layers of the mouse medial prefrontal cortex
Kroon, T., van Hugte, E., van Linge, L., Mansvelder, H. D., & Meredith, R. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-41661-9 · Cited by 161 · see citing works
Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine
Kim, I. H., Rossi, M. A., Aryal, D. K., Racz, B., Kim, N., Uezu, A., Wang, F., Wetsel, W. C., Weinberg, R. J., Yin, H., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4015 · Cited by 127 · see citing works
Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
“Furthermore, two-photon glutamate uncaging experiments on single spines indicate that synapses that already express functional AMPARs can be further enhanced by inducing LTP (246 – 248).”
BackgroundBarnes, S. A., Wijetunge, L. S., Jackson, A. D., Katsanevaki, D., Osterweil, E. K., Komiyama, N. H., Grant, S. G. N., Bear, M. F., Nägerl, U. V., Kind, P. C., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1087-15.2015 · Cited by 84 · see citing works
Self-citationControl of dendritic spine morphological and functional plasticity by small GTPases.
Woolfrey, K. M., & Srivastava, D. P. (2016) · Neural Plasticity · doi:10.1155/2016/3025948 · Cited by 76 · see citing works
Barriers in the brain: resolving dendritic spine morphology and compartmentalization
Adrian, M., Kusters, R., Wierenga, C. J., Storm, C., Hoogenraad, C. C., & Kapitein, L. C. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00142 · Cited by 62 · see citing works
“Most recently, STED microscopy on dendritic spines in organotypic and acute slices suggested that electric compartmentalization is moderate, but not absent, in most spines (Takasaki and Sabatini, 2014; Tønnesen et al., 2014).”
InfluentialPrincipal cell activity induces spine relocation of adult-born interneurons in the olfactory bulb
Breton-Provencher, V., Bakhshetyan, K., Hardy, D., Bammann, R. R., Cavarretta, F., Snapyan, M., Côté, D., Migliore, M., & Saghatelyan, A. (2016) · Nature Communications · doi:10.1038/ncomms12659 · Cited by 60 · see citing works
Synaptic memory survives molecular turnover
Lee, J., Chen, X., & Nicoll, R. A. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2211572119 · Cited by 27 · see citing works
- Authors
- Tønnesen, J., Katona, G., Rózsa, B., & Nägerl, U. V.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- HUN-REN Institute of Experimental Medicine (HU)
- Corresponding author
- Nägerl, U Valentin
- Venue
- Nature Neuroscience
- Published
- 2014-03-23
- Volume
- 17
- Issue
- 5
- Pages
- 678-685
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2033125075
- Cited by
- 444
- References
- 11
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 31 · 2023: 45 · 2022: 30 · 2021: 35 · 2020: 36 · 2019: 29 · 2018: 43 · 2017: 37 · 2016: 51 · 2015: 41 · 2014: 16
- FWCI
- 22.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-10-INBS-0004)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dendritic spines, dendritic spine morphology, CA1 pyramidal neurons, long-term potentiation, excitatory postsynaptic potentials, glutamate uncaging, FRAP
- MeSH terms
- Animals, Animals, Newborn, Bacterial Proteins, Luminescent Proteins, Mice, Transgenic, Neuronal Plasticity, Neurons, Organ Culture Techniques, Synapses, Electric Impedance, Long-Term Potentiation, Patch-Clamp Techniques, Microscopy, Confocal, Statistics, Nonparametric, Photobleaching, Dendritic Spines, Mice, Biophysical Phenomena, CA1 Region, Hippocampal
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
