The postsynaptic density in excitatory synapses is composed of clustered, heterogeneous nanoblocks
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Abstract
Abstract The nanoscale organization of proteins within synapses is critical for maintaining and regulating synaptic transmission and plasticity. Here, we use cryogenic electron tomography to directly visualize the three-dimensional architecture and supramolecular organization of pre-cleft-postsynaptic components in their near-native cellular context in both synaptosomes from rat hippocampi and synapses from rat primary cultured neurons. High-resolution electron microscopy and quantitative analyses revealed that postsynaptic density (PSD) is composed of membrane-associated nanoblocks of various sizes, which are in close relationship with potential presynaptic release sites through adhesion molecules spanning the synaptic cleft, as well as with post-synaptic receptors. Subtomogram averaging from synaptosomes showed two distinct types of postsynaptic membrane proteins at resolutions of 24 Å and 26 Å respectively. Furthermore, our data reveal that majority of potential release sites and ∼50% subtomogram averaged receptor-like particles are located within the boundary of PSD nanoblocks, while PSD nanoblocks might be redundant for neurotransmission. The results of this study provide a more comprehensive understanding of synaptic ultrastructure and suggest that PSD is composed of clustering of various nanoblocks, which likely underlies the dynamic nature of PSD to modulate synaptic strength.
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The postsynaptic density (PSD) serves as a protein hub where scaffolds such as PSD-95, shank, homer, and gephyrin anchor excitatory (AMPA, NMDA) and inhibitory (GABA-A, Glycine) receptors.
“Postsynaptically, the postsynaptic density (PSD) serves as a protein hub where scaffolds such as PSD-95, shank, homer, and gephyrin anchor excitatory (AMPA, NMDA) and inhibitory (GABA-A, Glycine) receptors are observed.”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [36]
The Introduction describes the PSD at excitatory synapses and identifies PSD95 as a postsynaptic scaffolding protein aligned with clustered AMPA receptors. The Results and discussion mention NMDA receptors only as a possible component of some nanoblocks. Our copy does not support the claimed roles of shank, homer, or gephyrin in anchoring the listed receptors, particularly GABA-A and glycine receptors at inhibitory synapses. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDuring a single LTP event, heterogeneity is resolved through rapid structural remodeling where 'nascent zones' are converted into functional active zones within 5 min via recruitment of dense-core vesicles.
“During a single LTP event, this heterogeneity is resolved through rapid structural remodeling where ‘nascent zones’ are converted into functional active zones within 5 min via the recruitment of dense-core vesicles, representing a high turnover rate of these nanoblocks to saturate potentiation capacity [36,37].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [36]
The Results and discussion section reports heterogeneous postsynaptic nanoblocks and possible unoccupied release sites. It does not report a single LTP event, conversion of nascent zones into active zones within 5 minutes, or recruitment of dense-core vesicles; searches for those terms found no supporting passage. Our copy provides no page numbers for these sections. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCryo-electron tomography studies have revealed that the PSD is composed of clustered, heterogeneous nanoblocks that vary in size, assembly, and distribution, containing type A (O-shaped) and type B (Y-shaped) receptor-like particles.
“Cryo-electron tomography studies have revealed that the PSD is not a monolithic structure but is composed of clustered, heterogeneous nanoblocks that vary in size, assembly, and distribution [36]. Nanoblocks contains two specific types of receptor-like particles, type A (O-shaped) and type B (Y-shaped) [36].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [36]
Presynaptic release sites align preferentially with nanoblocks containing A/B particles, while nanoblocks lacking them may serve as spare scaffolds or house other receptors.
“Presynaptic release sites align preferentially with nanoblocks containing these A/B particles, while nanoblocks lacking them may serve as spare scaffolds or house other receptors [36].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [36]
The postsynaptic density (PSD) is a highly organized, electron-dense protein complex situated directly beneath the postsynaptic membrane of excitatory synapses, typically at the tip of dendritic spines.
“The postsynaptic density (PSD) is a highly organized, electron-dense protein complex situated directly beneath the postsynaptic membrane of excitatory synapses [36]. This structure, typically found at the tip of dendritic spines, serves as a crucial hub for signal reception, transduction, and synaptic plasticity.”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [36]
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Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
(1996) · Cited by 20,179 · see citing works
MotionCor2 - anisotropic correction of beam-induced motion for improved cryo-electron microscopy
Zheng, S., Palovcak, E. J., Armache, J., Verba, K., Cheng, Y.-F., & Agard, D. (2017) · Nature Methods · doi:10.1038/nmeth.4193 · Cited by 7,678 · see citing works
Computer visualization of three-dimensional image data using IMOD.
Kremer, J. R., Mastronarde, D., & Mcintosh, J. (1996) · Journal of Structural Biology · doi:10.1006/jsbi.1996.0013 · Cited by 5,770 · see citing works
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568 · see citing works
Gctf: Real-time CTF determination and correction
Zhang, K. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.11.003 · Cited by 3,372 · see citing works
Gray, E. G., & Whittaker, V. P. (1962) · PubMed · Cited by 2,530 · see citing works
Cryo-electron microscopy of vitrified specimens
Dubochet, J., Adrian, M., Chang, J.-J., Homo, J., Lepault, J., McDowall, A. W., & Schultz, P. (1988) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500004297 · Cited by 2,397 · see citing works
Proteomic analysis of NMDA receptor–adhesion protein signaling complexes
Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P., & Grant, S. G. N. (2000) · Nature Neuroscience · doi:10.1038/76615 · Cited by 1,194 · see citing works
The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View
Sheng, M., & Hoogenraad, C. C. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060805.160029 · Cited by 1,003 · see citing works
Hagen, W. J. H., Wan, W., & Briggs, J. A. G. (2016) · Journal of Structural Biology · doi:10.1016/j.jsb.2016.06.007 · Cited by 812 · see citing works
A trans-synaptic nanocolumn aligns neurotransmitter release to receptors
Tang, A.-H., Chen, H., Li, T. P., Metzbower, S. R., MacGillavry, H. D., & Blanpied, T. A. (2016) · Nature · doi:10.1038/nature19058 · Cited by 677 · see citing works
SYNAPSES IN THE CENTRAL NERVOUS SYSTEM
Palay, S. L. (1956) · The Journal of Cell Biology · doi:10.1083/jcb.2.4.193 · Cited by 634 · see citing works
Nair, D., Hosy, E., Petersen, J. D., Constals, A., Giannone, G., Choquet, D., & Sibarita, J.-B. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2381-12.2013 · Cited by 617 · see citing works
The Postsynaptic Organization of Synapses
Sheng, M., & Kim, E. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005678 · Cited by 603 · see citing works
Zeng, M., Shang, Y., Araki, Y., Guo, T., Huganir, R. L., & Zhang, M. (2016) · Cell · doi:10.1016/j.cell.2016.07.008 · Cited by 598 · see citing works
Electron Diffraction of Frozen, Hydrated Protein Crystals
Taylor, K. A., & Glaeser, R. M. (1974) · Science · doi:10.1126/science.186.4168.1036 · Cited by 443 · see citing works
Nanoscale Scaffolding Domains within the Postsynaptic Density Concentrate Synaptic AMPA Receptors
MacGillavry, H. D., Song, Y., Raghavachari, S., & Blanpied, T. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.03.009 · Cited by 442 · see citing works
Zeng, M., Chen, X., Guan, D., Xu, J., Wu, H., Tong, P., & Zhang, M. (2018) · Cell · doi:10.1016/j.cell.2018.06.047 · Cited by 438 · see citing works
Ultrastructure of Synapses in the Mammalian BrainPreprint
Harris, K. M., & Weinberg, R. J. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005587 · Cited by 423 · see citing works
Hollingsworth, E. B., McNeal, E., Burton, J. L., Williams, R., Daly, J. W., & Creveling, C. R. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-08-02240.1985 · Cited by 408 · see citing works
Proteomic Analysis of Unbounded Cellular Compartments: Synaptic Clefts
Loh, K. H., Stawski, P. S., Draycott, A. S., Udeshi, N. D., Lehrman, E. K., Wilton, D. K., Svinkina, T., Deerinck, T. J., Ellisman, M. H., Stevens, B., et al. (2016) · Cell · doi:10.1016/j.cell.2016.07.041 · Cited by 399 · see citing works
Structural and Functional Architecture of AMPA-Type Glutamate Receptors and Their Auxiliary Proteins
Greger, I. H., Watson, J. F., & Cull-Candy, S. G. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.009 · Cited by 392 · see citing works
Quinlan, E. M., Olstein, D. H., & Bear, M. F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12876 · Cited by 382 · see citing works
Isotropic reconstruction for electron tomography with deep learning
Liu, Y.-T., Zhang, H., Wang, H., Tao, C.-L., Bi, G., & Zhou, Z. H. (2022) · Nature Communications · doi:10.1038/s41467-022-33957-8 · Cited by 355 · see citing works
Self-citationTranscellular Nanoalignment of Synaptic Function
Biederer, T., Kaeser, P. S., & Blanpied, T. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.10.006 · Cited by 352 · see citing works
Electron tomography of molecules and cells
Baumeister, W. (1999) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01423-8 · Cited by 343 · see citing works
The promise and the challenges of cryo‐electron tomography
Turk, M., & Baumeister, W. P. (2020) · FEBS Letters · doi:10.1002/1873-3468.13948 · Cited by 336 · see citing works
Chen, X., Levy, J. M., Hou, A., Winters, C., Azzam, R., Sousa, A. A., Leapman, R. D., Nicoll, R. A., & Reese, T. S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1517045112 · Cited by 310 · see citing works
PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density
Chen, X., Nelson, C. D., Li, X., Winters, C. A., Azzam, R. N., Sousa, A. A., Leapman, R. D., Gainer, H., Sheng, M., & Reese, T. S. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5968-10.2011 · Cited by 304 · see citing works
Organization of the core structure of the postsynaptic density
Chen, X., Winters, C. A., Azzam, R. N., Li, X., Galbraith, J. A., Leapman, R. D., & Reese, T. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800897105 · Cited by 290 · see citing works
Fernández, E., Collins, M. O., Uren, R. T., Kopanitsa, M. V., Komiyama, N. H., Croning, M. D. R., Zografos, L., Armstrong, J. D., Choudhary, J. S., & Grant, S. G. N. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.27 · Cited by 275 · see citing works
Quantitative analysis of the native presynaptic cytomatrix by cryoelectron tomography
Fernández-Busnadiego, R., Zuber, B., Maurer, U. E., Cyrklaff, M., Baumeister, W., & Lučić, V. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200908082 · Cited by 267 · see citing works
Bharat, T. A. M., & Scheres, S. H. W. (2016) · Nature Protocols · doi:10.1038/nprot.2016.124 · Cited by 262 · see citing works
Synaptic nanomodules underlie the organization and plasticity of spine synapses
Hruska, M., Henderson, N., Le Marchand, S. J., Jafri, H., & Dalva, M. B. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0138-9 · Cited by 233 · see citing works
Structural mechanism of glutamate receptor activation and desensitization
Meyerson, J. R., Kumar, J., Chittori, S., Rao, P., Pierson, J., Bartesaghi, A., Mayer, M. L., & Subramaniam, S. (2014) · Nature · doi:10.1038/nature13603 · Cited by 227 · see citing works
Petersen, J. D., Chen, X., Vinadé, L., Döṣemeci, A., Lisman, J. E., & Reese, T. S. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-35-11270.2003 · Cited by 211 · see citing works
Tao, C.-L., Liu, Y.-T., Sun, R., Zhang, B., Qi, L., Shivakoti, S., Tian, C.-L., Zhang, P., Lau, P.-M., Zhou, Z. H., et al. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.1548-17.2017 · Cited by 207 · see citing works
Self-citationGeinisman, Y., Detoledo‐Morrell, L., Morrell, F., Heller, R. E., Rossi, M. A., & Parshall, R. F. (1993) · Hippocampus · doi:10.1002/hipo.450030405 · Cited by 206 · see citing works
Structure and Dynamics of AMPA Receptor GluA2 in Resting, Pre-Open, and Desensitized States
Dürr, K. L., Chen, L., Stein, R. A., Zorzi, R. D., Folea, I. M., Walz, T., Mchaourab, H. S., & Gouaux, E. (2014) · Cell · doi:10.1016/j.cell.2014.07.023 · Cited by 200 · see citing works
Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM
Zhao, Y., Chen, S., Swensen, A., Qian, W., & Gouaux, E. (2019) · Science · doi:10.1126/science.aaw8250 · Cited by 198 · see citing works
Pre-post synaptic alignment through neuroligin-1 tunes synaptic transmission efficiency
Haas, K. T., Compans, B., Letellier, M., Bartol, T. M., Grillo-Bosch, D., Sejnowski, T. J., Sainlos, M., Choquet, D., Thoumine, O., & Hosy, E. (2018) · eLife · doi:10.7554/elife.31755 · Cited by 183 · see citing works
PSD95 nanoclusters are postsynaptic building blocks in hippocampus circuits
Broadhead, M. J., Horrocks, M. H., Zhu, F., Mureşan, L., Benavides‐Piccione, R., DeFelipe, J., Fricker, D. G., Kopanitsa, M. V., Duncan, R. R., Klenerman, D., et al. (2016) · Scientific Reports · doi:10.1038/srep24626 · Cited by 173 · see citing works
Composition of the Synaptic PSD-95 Complex
Döṣemeci, A., Makusky, A. J., Jankowska‐Stephens, E., Yang, X., Slotta, D. J., & Markey, S. P. (2007) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700040-mcp200 · Cited by 172 · see citing works
Frank, R., Komiyama, N. H., Ryan, T. J., Zhu, F., O’Dell, T. J., & Grant, S. G. N. (2016) · Nature Communications · doi:10.1038/ncomms11264 · Cited by 169 · see citing works
Perforated postsynaptic densities: probable intermediates in synapse turnover.
Nieto‐Sampedro, M., Hoff, S. F., & Cotman, C. W. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.18.5718 · Cited by 161 · see citing works
Chamma, I., Letellier, M., Butler, C., Tessier, B., Lim, K. H., Gauthereau, I., Choquet, D., Sibarita, J., Park, S., Sainlos, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms10773 · Cited by 159 · see citing works
The energy dependence of contrast and damage in electron cryomicroscopy of biological molecules
Peet, M. J., Henderson, R. A., & Russo, C. J. (2019) · Ultramicroscopy · doi:10.1016/j.ultramic.2019.02.007 · Cited by 154 · see citing works
The cell in absence of aggregation artifacts
Dubochet, J., & Blanc, N. S. (2001) · Micron · doi:10.1016/s0968-4328(00)00026-3 · Cited by 147 · see citing works
The Postsynaptic Density: There Is More than Meets the Eye
Dosemeci, A., Weinberg, R. J., Reese, T. S., & Tao-Cheng, J.-H. (2016) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2016.00023 · Cited by 138 · see citing works
The proteomic landscape of synaptic diversity across brain regions and cell types
van Oostrum, M., Blok, T. M., Giandomenico, S. L., tom Dieck, S., Tushev, G., Fürst, N., Langer, J. D., & Schuman, E. M. (2023) · Cell · doi:10.1016/j.cell.2023.09.028 · Cited by 135 · see citing works
Husi, H., & Grant, S. G. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00248.x · Cited by 134 · see citing works
Postsynaptic density proteins and their involvement in neurodevelopmental disorders
Kaizuka, T., & Takumi, T. (2018) · The Journal of Biochemistry · doi:10.1093/jb/mvy022 · Cited by 131 · see citing works
Cryo–electron tomography reveals a critical role of RIM1α in synaptic vesicle tethering
Fernández‐Busnadiego, R., Asano, S. M., Oprişoreanu, A., Sakata, E., Doengi, M., Kochovski, Z., Zürner, M., Stein, V., Schoch, S., Baumeister, W. P., et al. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201206063 · Cited by 128 · see citing works
Nanoscale Subsynaptic Domains Underlie the Organization of the Inhibitory Synapse
Crosby, K. C., Gookin, S. E., Garcia, J. D., Zent, K. H., Dell’Acqua, M. L., & Smith, K. R. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.070 · Cited by 126 · see citing works
Kellermayer, B., Ferreira, J. S., Dupuis, J. P., Levet, F., Grillo‐Bosch, D., Bard, L., Linarès-Loyez, J., Bouchet, D., Choquet, D., Rusakov, D. A., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.012 · Cited by 125 · see citing works
Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains
de Arce, K. P., Schrod, N., Metzbower, S. R., Allgeyer, E. S., Kong, G. K.-W., Tang, A., Krupp, A. J., Stein, V., Liu, X., Bewersdorf, J., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.11.011 · Cited by 124 · see citing works
Supramolecular organization of NMDA receptors and the postsynaptic density
Frank, R., & Grant, S. G. N. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.05.019 · Cited by 119 · see citing works
Pennacchietti, F., Vascon, S., Nieus, T. R., Rosillo, C., Das, S., Tyagarajan, S. K., Diaspro, A., Bue, A. D., Petrini, E. M., Barberis, A., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0514-16.2016 · Cited by 112 · see citing works
Morphological Characterization of Molecular Complexes Present in the Synaptic Cleft
́, V. L., Yang, T., Schweikert, G., Förster, F. G., & Baumeister, W. P. (2005) · Structure · doi:10.1016/j.str.2005.02.005 · Cited by 109 · see citing works
Stewart, M. G., Medvedev, N. I., Popov, V. I., Schoepfer, R., Davies, H. A., Murphy, K., Dallérac, G. M., Kraev, I., & Rodríguez, J. J. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04174.x · Cited by 93 · see citing works
Rahbek‐Clemmensen, T., Lycas, M. D., Erlendsson, S., Eriksen, J., Apuschkin, M., Vilhardt, F., Jørgensen, T. N., Herborg, F., & Gether, U. (2017) · Nature Communications · doi:10.1038/s41467-017-00790-3 · Cited by 91 · see citing works
Subsynaptic positioning of AMPARs by LRRTM2 controls synaptic strength
Ramsey, A. M., Tang, A., LeGates, T. A., Gou, X., Carbone, B. E., Thompson, S. M., Biederer, T., & Blanpied, T. A. (2021) · Science Advances · doi:10.1126/sciadv.abf3126 · Cited by 90 · see citing works
Nanoscale Structural Plasticity of the Active Zone Matrix Modulates Presynaptic Function
Glebov, O. O., Jackson, R. E., Winterflood, C. M., Owen, D. M., Barker, E. A., Doherty, P., Ewers, H., & Burrone, J. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.064 · Cited by 88 · see citing works
Spatiotemporal Regulation of Synaptic Vesicle Fusion Sites in Central Synapses
Maschi, D., & Klyachko, V. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.006 · Cited by 86 · see citing works
Electron tomographic analysis of synaptic ultrastructure
Burette, A. C., Lesperance, T., Crum, J., Martone, M., Volkmann, N., Ellisman, M. H., & Weinberg, R. J. (2012) · Journal of Comparative Neurology · doi:10.1002/cne.23067 · Cited by 85 · see citing works
Subsynaptic spatial organization as a regulator of synaptic strength and plasticity
Chen, H., Tang, A., & Blanpied, T. A. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.05.004 · Cited by 84 · see citing works
Role of Aberrant Spontaneous Neurotransmission in SNAP25-Associated Encephalopathies
Alten, B., Zhou, Q., Shin, O., Esquivies, L. R., Lin, P.-Y., White, K. I., Sun, R., Chung, W. K., Monteggia, L. M., Brünger, A. T., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.10.012 · Cited by 76 · see citing works
Self-citationProteomics of the Synapse – A Quantitative Approach to Neuronal Plasticity
Dieterich, D. C., & Kreutz, M. R. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r115.051482 · Cited by 73 · see citing works
Dutta, A., Krieger, J., Lee, J. Y., García‐Nafría, J., Greger, I. H., & Bahar, İ. (2015) · Structure · doi:10.1016/j.str.2015.07.002 · Cited by 72 · see citing works
Comparison of different methods for thin section EM analysis of Mycobacterium smegmatis
Bleck, C. K. E., MERZ, A., Gutierrez, M. G., Walther, P., Dubochet, J., Zuber, B., & GRIFFITHS, G. (2009) · Journal of Microscopy · doi:10.1111/j.1365-2818.2009.03299.x · Cited by 71 · see citing works
Phase separation as a mechanism for assembling dynamic postsynaptic density signalling complexes
Feng, Z., Chen, X., Zeng, M., & Zhang, M. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.12.001 · Cited by 68 · see citing works
Trans-synaptic assemblies link synaptic vesicles and neuroreceptors
Martínez-Sánchez, A., Laugks, U., Kochovski, Z., Papantoniou, C., Zinzula, L., Baumeister, W. P., & Lučić, V. (2021) · Science Advances · doi:10.1126/sciadv.abe6204 · Cited by 62 · see citing works
Frank, R., Zhu, F., Komiyama, N. H., & Grant, S. G. N. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14056 · Cited by 60 · see citing works
Distribution of the scaffolding proteins PSD-95, PSD-93, and SAP97 in isolated PSDs
DeGiorgis, J. A., Galbraith, J. A., Döṣemeci, A., Chen, X., & Reese, T. S. (2006) · Journal of Neurocytology · doi:10.1007/s11068-007-9017-0 · Cited by 60 · see citing works
Hruska, M., Cain, R. E., & Dalva, M. B. (2022) · Nature Communications · doi:10.1038/s41467-022-28504-4 · Cited by 56 · see citing works
Held, R. G., Liang, J., & Brünger, A. T. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2403136121 · Cited by 51 · see citing works
Three-dimensional structure of an AMPA receptor without associated stargazin/TARP proteins
Nakagawa, T., Cheng, Y., Sheng, M., & Walz, T. (2006) · Biological Chemistry · doi:10.1515/bc.2006.024 · Cited by 45 · see citing works
Nano-Organization at the Synapse: Segregation of Distinct Forms of Neurotransmission
Guzikowski, N. J., & Kavalali, E. T. (2021) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2021.796498 · Cited by 45 · see citing works
PDZ Ligand Binding-Induced Conformational Coupling of the PDZ–SH3–GK Tandems in PSD-95 Family MAGUKs
Zeng, M., Ye, F., Xu, J., & Zhang, M. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.11.003 · Cited by 44 · see citing works
The Synaptosome as a Model System for Studying Synaptic PhysiologyPreprint
Evans, G. J. (2015) · Cold Spring Harbor Protocols · doi:10.1101/pdb.top074450 · Cited by 40 · see citing works
The dynamic AMPA receptor extracellular region: a platform for synaptic protein interactions
García‐Nafría, J., Herguedas, B., Watson, J. F., & Greger, I. H. (2016) · The Journal of Physiology · doi:10.1113/jp271844 · Cited by 40 · see citing works
Structure, Dynamics, and Allosteric Potential of Ionotropic Glutamate Receptor N-Terminal Domains
Krieger, J., Bahar, İ., & Greger, I. H. (2015) · Biophysical Journal · doi:10.1016/j.bpj.2015.06.061 · Cited by 36 · see citing works
Nanoscale Organization of Vesicle Release at Central Synapses
Gramlich, M. W., & Klyachko, V. A. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.03.001 · Cited by 35 · see citing works
Khavnekar, S., Erdmann, P. S., & Wan, W. (2024) · Journal of Applied Crystallography · doi:10.1107/s1600576724010264 · Cited by 33 · see citing works
Affinity purification of PSD‐95‐containing postsynaptic complexes
Vinadé, L., Chang, M., Schlief, M. L., Petersen, J. D., Reese, T. S., Tao-Cheng, J.-H., & Döṣemeci, A. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02091.x · Cited by 31 · see citing works
The role of postsynaptic density proteins in neural degeneration and regeneration
Montgomery, J., & Vyas, Y. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.184481 · Cited by 29 · see citing works
Gylys, K. H., & Bilousova, T. V. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6598-4_16 · Cited by 27 · see citing works
Spatially non-overlapping Ca2+ signals drive distinct forms of neurotransmission
Wang, C. S., Monteggia, L. M., & Kavalali, E. T. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113201 · Cited by 23 · see citing works
Sun, R., Liu, Y.-T., Tao, C.-L., Qi, L., Lau, P.-M., Zhou, Z. H., & Bi, G. (2019) · Biophysics Reports · doi:10.1007/s41048-019-0092-4 · Cited by 19 · see citing works
Self-citationNia, F. H., Woike, D., Bento, I., Niebling, S., Tibbe, D., Schulz, K., Hirnet, D., Skiba, M., Hönck, H., Veith, K., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01882-3 · Cited by 18 · see citing works
wan-lab-vanderbilt/TOMOMAN: TOMOMAN 0.9
Wan, W. (2020) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.4110736 · Cited by 11 · see citing works
CryoVesNet: A dedicated framework for synaptic vesicle segmentation in cryo-electron tomograms
Khosrozadeh, A., Seeger, R., Witz, G., Radecke, J., Sørensen, J. B., & Zuber, B. (2024) · The Journal of Cell Biology · doi:10.1083/jcb.202402169 · Cited by 10 · see citing works
Jung, J. H., Chen, X., & Reese, T. S. (2023) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2023.1123564 · Cited by 9 · see citing works
Super-resolution imaging of synaptic scaffold proteins in rat hippocampal neurons
Guzikowski, N. J., & Kavalali, E. T. (2023) · STAR Protocols · doi:10.1016/j.xpro.2023.102080 · Cited by 3 · see citing works
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Sorted by citations
Activity-dependent diffusion trapping of AMPA receptors as a key step for expression of early LTP
Nowacka, A., Getz, A. M., Bessa‐Neto, D., & Choquet, D. (2024) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2023.0220 · Cited by 19 · see citing works
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Xu, N., Chen, S.-Y., & Tang, A. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2024.12.009 · Cited by 10 · see citing works
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Ramírez-Expósito, M. J., Cueto-Ureña, C., & Martínez-Martos, J. M. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48010088 · Cited by 6 · see citing works
“Nanoblocks contains two specific types of receptor-like particles, type A (O-shaped) and type B (Y-shaped) [36].”
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Petrovic, A., Do, T. T., & Fernández-Busnadiego, R. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2024.102939 · Cited by 4 · see citing works
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Fujise, K., Mishra, J., Karmali, N., & Rafiq, N. M. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.09.011 · Cited by 3 · see citing works
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Tian, C.-L., Qi, L., Lu, Z.-H., Liu, S., Gu, M., Huang, W.-L., Yan, Y.-T., Liu, Y., Wu, J., Wang, P., et al. (2026) · Neuroscience Bulletin · doi:10.1007/s12264-025-01569-z · Cited by 3 · see citing works
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Damenti, M., Levy, A. D., & Blanpied, T. A. (2026) · Advances in neurobiology · doi:10.1007/978-3-032-12594-1_7 · Cited by 2 · see citing works
Transsynaptic linking of calcium channels and postsynaptic receptors at a dyadic synapse
Zhao, J., Ardiel, E. L., Nurrish, S., & Kaplan, J. M. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2603452123 · Cited by 2 · see citing works
Jia, T., Jian, H., Wang, Y., Li, C., Hua, Y., & Bai, Y. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.11.032 · Cited by 1 · see citing works
Visualizing Postsynaptic Density in Excitatory Synapses with Electron Tomography
Sun, R., & Zhou, Q. (2026) · Advances in neurobiology · doi:10.1007/978-3-032-12594-1_10 · Cited by 1 · see citing works
Self-citationA Brainwide Atlas of Synaptic Nanoarchitecture Across the Mouse LifespanPreprint
Kaizuka, T., Qiu, Z., Bulovaite, E., Morris, K., Zhao, T., Adams, C., Varga, G., Dominic, D., Komiyama, N. H., Horrocks, M. H., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.18.706606 · Cited by 1 · see citing works
Ultrafast Isolation of Synaptic Terminals From Rat Brain for Cryo-Electron Tomography Analysis
Sun, R., & Zhou, Q. (2025) · BIO-PROTOCOL · doi:10.21769/bioprotoc.5429
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Bandekar, S. J., Kordon, S. P., & Araç, D. (2026) · Advances in neurobiology · doi:10.1007/978-3-032-12594-1_6 · Cited by 1 · see citing works
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Rothfuss, S. J., & Zhou, Q. (2026) · Structure · doi:10.1016/j.str.2026.04.008
Self-citationMachala, E. A., & Baker, L. A. (2026) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2026.103292
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(134879), K. X., Wu, S., & Zhu, S. (2026) · Trends in Neurosciences · doi:10.1016/j.tins.2026.05.004
Acharjee, A., Rai, N., Patel, A., & Acharjee, P. (2026) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2026.141169
Lu, C., Wang, Y., Dai, G., Ju, W., Sun, Y., Zhang, H., & Wu, L. (2026) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2026.107012
Nonequilibrium Interfacial Complexation Fibers With Programmable Ionic Memory
Li, T., Bong, J. H., Nikolaev, K. G., Chen, H., Wen, X., Siriaraya, P., Kuwahara, N., Karim, N., Novoselov, K. S., & Andreeva, D. V. (2026) · Advanced Materials · doi:10.1002/adma.74913
Cryo-electron tomography of functionally validated synapses in human induced neurons
Houcek, A., Sun, R., Rothfuss, S. J., Chalkley, O. R., Kavalali, E. T., & Zhou, Q. (2026) · Structure · doi:10.1016/j.str.2026.08.014
Self-citation
- Authors
- Sun, R., Allen, J. P., Mao, Z., Wilson, L., Haider, M., Alten, B., Zhou, Z., Wang, X., & Zhou, Q.
- Affiliations
- Vanderbilt University (US)
- Vanderbilt University 4 Department of Pharmacology, , Nashville, TN,
- Corresponding author
- Zhou, Qiangjun
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2025-03-27
- Volume
- 224
- Issue
- 6
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC11948668
- OpenAlex
- W4408908092
- Cited by
- 20
- References
- 95
- Citations by year
- 2026: 14 · 2025: 4 · 2024: 2
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R00 MH113764, R01 MH132918, S10 OD030292-01)
- Vanderbilt Brain Institue (“Neurodegenerative” TIPS Initiative Award)
- Vanderbilt University
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- postsynaptic density, excitatory synapses, synaptic ultrastructure, synaptosomes, presynaptic release sites, synaptic plasticity, cryo-electron tomography
- MeSH terms
- Animals, Cells, Cultured, Synaptic Transmission, Neurons, Synapses, Synaptosomes, Cryoelectron Microscopy, Rats, Electron Microscope Tomography, Post-Synaptic Density
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