Synchronized Formation and Remodeling of Postsynaptic Densities: Long-Term Visualization of Hippocampal Neurons Expressing Postsynaptic Density Proteins Tagged with Green Fluorescent Protein
Open accessAbstract
To explore mechanisms governing the formation and remodeling of postsynaptic density (PSD), we used dissociated cultures of hippocampal neurons isolated from transgenic embryos expressing green fluorescent protein (GFP)-tagged PSD proteins PSD-Zip45 (Homer 1c) and PSD-95. Expression of GFP-tagged PSD molecules was stable, and the remodeling process of PSDs could be followed for >1 week. A higher expression level of GFP-PSD-Zip45 enabled us to quantitatively analyze the amount of PSD-Zip45 clusters during development. Repetitive imaging of the same cell populations between 11 and 17 d in culture revealed an increase of the average PSD-Zip45 cluster density from 0.32 to 0.73/μm. Newly generated dendrites rapidly acquired GFP-PSD-Zip45 clusters, and their density reached the level of parental dendrites within a few days. Temporal profiles of GFP-PSD-Zip45 cluster density showed a variety of patterns. Some dendrites showed a monotonous increase of clusters, whereas others showed complex patterns, including short decremental stages. Analysis of long-term remodeling of PSD-95-GFP clusters confirmed that the decremental stages were not specific to the PSD-Zip45 clusters. Comparison of the temporal profiles of the cluster density among neurons indicated synchronization of both GFP-PSD-Zip45 and PSD-95 clustering within individual cells. Furthermore, activation of cAMP-dependent protein kinase suppressed the decremental stages of cluster remodeling. These observations suggest the presence of signaling mechanisms that can induce synchronized addition or elimination of PSD proteins throughout dendritic arborization of a single neuron.
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Cites
Activity-dependent scaling of quantal amplitude in neocortical neurons
Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C., & Nelson, S. B. (1998) · Nature · doi:10.1038/36103 · Cited by 2,226 · see citing works
Dendritic spine changes associated with hippocampal long-term synaptic plasticity
Engert, F., & Bonhoeffer, T. (1999) · Nature · doi:10.1038/19978 · Cited by 1,664 · see citing works
Hayashi, Y., Shi, S.-H., Esteban, J. A., Piccini, A., Poncer, J.-C., & Malinow, R. (2000) · Science · doi:10.1126/science.287.5461.2262 · Cited by 1,524 · 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
Rapid Spine Delivery and Redistribution of AMPA Receptors After Synaptic NMDA Receptor Activation
Shi, S.-H., Hayashi, Y., Petralia, R. S., Zaman, S. H., Wenthold, R. J., Svoboda, K., & Malinow, R. (1999) · Science · doi:10.1126/science.284.5421.1811 · Cited by 1,276 · see citing works
PDZ Domains and the Organization of Supramolecular Complexes
Sheng, M., & Sala, C. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1 · Cited by 1,191 · see citing works
Rapid Dendritic Morphogenesis in CA1 Hippocampal Dendrites Induced by Synaptic Activity
Maletić‐Savatić, M., Malinow, R., & Svoboda, K. (1999) · Science · doi:10.1126/science.283.5409.1923 · Cited by 1,189 · see citing works
Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity
Lee, H.-K., Barbarosie, M., Kameyama, K., Bear, M. F., & Huganir, R. L. (2000) · Nature · doi:10.1038/35016089 · Cited by 1,116 · see citing works
Homer: a protein that selectively binds metabotropic glutamate receptors
Brakeman, P., Lanahan, A. A., O’Brien, R., Roche, K. W., Barnes, C. A., Huganir, R. L., & Worley, P. F. (1997) · Nature · doi:10.1038/386284a0 · Cited by 1,115 · 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
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
Miyake, S., Makimura, M., Kanegae, Y., Harada, S., Sato, Y., Takamori, K., Tokuda, C., & Saito, I. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.3.1320 · Cited by 788 · see citing works
Signal-Processing Machines at the Postsynaptic Density
Kennedy, M. B. (2000) · Science · doi:10.1126/science.290.5492.750 · Cited by 788 · see citing works
Regulation of Dendritic Spine Morphology and Synaptic Function by Shank and Homer
Sala, C., Piëch, V., Wilson, N. R., Passafaro, M., Liu, G., & Sheng, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00339-7 · Cited by 716 · see citing works
Shen, K., & Meyer, T. (1999) · Science · doi:10.1126/science.284.5411.162 · Cited by 673 · see citing works
Xiao, B., Tu, J. C., Petralia, R. S., Yuan, J. P., Doan, A., Breder, C. D., Ruggiero, A. M., Lanahan, A. A., Wenthold, R. J., & Worley, P. F. (1998) · Neuron · doi:10.1016/s0896-6273(00)80588-7 · Cited by 649 · 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
Kanegae, Y., Lee, G., Sato, Y., Tanaka, M., Nakal, M., Sakaki, T., Sugano, S., & Saito, I. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.19.3816 · Cited by 606 · see citing works
Assembly of presynaptic active zones from cytoplasmic transport packets
Ahmari, S. E., Buchanan, J., & Smith, S. J. (2000) · Nature Neuroscience · doi:10.1038/74814 · Cited by 596 · see citing works
Synaptic Strength Regulated by Palmitate Cycling on PSD-95
El-Husseini, A., Schnell, E., Dakoji, S., Sweeney, N. T., Zhou, Q., Prange, O., Gauthier-Campbell, C., Aguilera-Moreno, A., Nicoll, R. A., & Bredt, D. S. (2002) · Cell · doi:10.1016/s0092-8674(02)00683-9 · Cited by 569 · see citing works
Activity Regulates the Synaptic Localization of the NMDA Receptor in Hippocampal Neurons
Rao, A., & Craig, A. M. (1997) · Neuron · doi:10.1016/s0896-6273(00)80962-9 · Cited by 492 · see citing works
A SIMPLE AND EFFICIENT METHOD FOR PURIFICATION OF INFECTIOUS RECOMBINANT ADENOVIRUS
Kanegae, Y., Makimura, M., & Saito, I. (1994) · Japanese Journal of Medical Science and Biology · doi:10.7883/yoken1952.47.157 · Cited by 444 · see citing works
Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons
Liao, D., Zhang, X., O’Brien, R., Ehlers, M., & Huganir, R. L. (1999) · Nature Neuroscience · doi:10.1038/4540 · Cited by 395 · see citing works
Regulation of Dendritic Spine Morphology by SPAR, a PSD-95-Associated RapGAP
Pak, D. T. S., Yang, S., Rudolph-Correia, S., Kim, E., & Sheng, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00355-5 · Cited by 386 · see citing works
Sparks, A. B., Rider, J. E., Hoffman, N. G., Fowlkes, D. M., Quillam, L. A., & Kay, B. K. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.4.1540 · Cited by 348 · see citing works
Lissin, D., Gomperts, S. N., Carroll, R. C., Christine, C. W., Kalman, D., Kitamura, M., Hardy, S. F., Nicoll, R. A., Malenka, R. C., & von Zastrow, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.7097 · Cited by 332 · see citing works
How do dendrites take their shape?
Scott, E. K., & Luo, L. (2001) · Nature Neuroscience · doi:10.1038/86006 · Cited by 292 · see citing works
Spine Formation and Correlated Assembly of Presynaptic and Postsynaptic Molecules
Okabe, S., Miwa, A., & Okado, H. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-16-06105.2001 · Cited by 291 · see citing works
Self-citationKameyama, K., Lee, H.-K., Bear, M. F., & Huganir, R. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)80633-9 · Cited by 283 · see citing works
Novel Members of the Vesl/Homer Family of PDZ Proteins That Bind Metabotropic Glutamate Receptors
Kato, A., Ozawa, F., Saitoh, Y., Fukazawa, Y., Sugiyama, H., & Inokuchi, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.37.23969 · Cited by 280 · see citing works
Continual remodeling of postsynaptic density and its regulation by synaptic activity
Okabe, S., Kim, H., Miwa, A., Kuriu, T., & Okado, H. (1999) · Nature Neuroscience · doi:10.1038/12175 · Cited by 257 · see citing works
Self-citationLissin, D., Carroll, R. C., Nicoll, R. A., Malenka, R. C., & von Zastrow, M. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-04-01263.1999 · Cited by 206 · see citing works
Vanderklish, P. W., & Edelman, G. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032681099 · Cited by 194 · see citing works
Gomez, L. L., Alam, S., Smith, K. E., Horne, E., & Dell'Acqua, M. L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-16-07027.2002 · Cited by 170 · see citing works
cAMP-Dependent Protein Kinase Mediates Activity-Regulated Synaptic Targeting of NMDA Receptors
Crump, F. T., Dillman, K. S., & Craig, A. M. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05079.2001 · Cited by 138 · see citing works
Tadokoro, S., Tachibana, T., Imanaka, T., Nishida, W., & Sobue, K. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.13801 · Cited by 130 · see citing works
Self-citationOrganization and regulation of proteins at synapses
Kim, J. H., & Huganir, R. L. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80033-7 · Cited by 127 · see citing works
Okabe, S., Urushido, T., Konno, D., Okado, H., & Sobue, K. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-24-09561.2001 · Cited by 119 · see citing works
Self-citationSun, J. Y., Tadokoro, S., Imanaka, T., et al. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01256-3 · Cited by 74 · see citing works
Fine structure of neurons and synapses in the feline hippocampus during postnatal ontogenesis
Schwartz, I. R., Pappas, G. D., & Purpura, D. P. (1968) · Experimental Neurology · doi:10.1016/0014-4886(68)90005-8 · Cited by 64 · see citing works
Phorbol esters promote postsynaptic accumulation of Vesl‐1S/Homer‐1a protein
Kato, A., Fukuda, T., Fukazawa, Y., Isojima, Y., Fujitani, K., Inokuchi, K., & Sugiyama, H. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01498.x · Cited by 34 · see citing works
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Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · see citing works
“To directly test whether phagocytic microglia engulf synaptic elements, we adapted our in vivo synaptic engulfment assay (19) using intracerebroventricular injections of Aβ in Homer-GFP mice (20) (Fig.”
Determination of absolute protein numbers in single synapses by a GFP-based calibration technique
Sugiyama, Y., Kawabata, I., Sobue, K., & Okabe, S. (2005) · Nature Methods · doi:10.1038/nmeth783 · Cited by 189 · see citing works
Self-citationSzumlinski, K. K., Lominac, K. D., Kleschen, M. J., Oleson, E. B., Dehoff, M. H., Schwartz, M. K., Seeberg, P. H., Worley, P. F., & Kalivas, P. W. (2005) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2005.00120.x · Cited by 181 · see citing works
Enhanced synapse remodelling as a common phenotype in mouse models of autism
Isshiki, M., Tanaka, S., Kuriu, T., Tabuchi, K., Takumi, T., & Okabe, S. (2014) · Nature Communications · doi:10.1038/ncomms5742 · Cited by 152 · see citing works
Self-citationFluorescence imaging of synapse formation and remodeling
Okabe, S. (2013) · Microscopy · doi:10.1093/jmicro/dfs083 · Cited by 26 · see citing works
Self-citation
- Authors
- Ebihara, T., Kawabata, I., Usui, S., Sobue, K., & Okabe, S.
- Affiliations
- National Institute of Advanced Industrial Science and Technology (JP)
- Tokyo Medical and Dental University (JP)
- The University of Osaka (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-03-15
- Volume
- 23
- Issue
- 6
- Pages
- 2170-2181
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6742042
- OpenAlex
- W1871421938
- Cited by
- 78
- References
- 41
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 6 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science and Technology Corporation
- Core Research for Evolutional Science and Technology
- 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
- postsynaptic density, PSD-95, dendritic branching, dendritic spine development, protein kinase A, hippocampal neurons, synaptic plasticity
- MeSH terms
- Homer Scaffolding Proteins, Disks Large Homolog 4 Protein, Cyclic AMP, Animals, Bacterial Proteins, Carrier Proteins, Cells, Cultured, Dendrites, Hippocampus, Luminescent Proteins, Membrane Proteins, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Neuropeptides, Recombinant Fusion Proteins, Synapses, Signal Transduction, Gene Expression Regulation, Developmental, Transgenes, Intracellular Signaling Peptides and Proteins, Green Fluorescent Proteins, Mice, Guanylate Kinases
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