Synaptogenesis Via Dendritic Filopodia in Developing Hippocampal Area CA1
Open accessAbstract
To determine the role of dendritic filopodia in the genesis of excitatory synaptic contacts and dendritic spines in hippocampal area CA1, serial section electron microscopy and three-dimensional analysis of 16 volumes of neuropil from nine male rat pups, aged postnatal day 1 (P1) through P12, were performed. The analysis revealed that numerous dendritic filopodia formed asymmetric synaptic contacts with axons and with filopodia extending from axons, especially during the first postnatal week. At P1, 22 ± 5.5% of synapses occurred on dendritic filopodia, with 19 ± 5.9% on filopodia at P4, 20 ± 8.0% at P6, decreasing to 7.2 ± 4.7% at P12 (p< 0.02). Synapses were found at the base and along the entire length of filopodia, with many filopodia exhibiting multiple synaptic contacts. In all, 162 completely traceable dendritic filopodia received 255 asymmetric synaptic contacts. These synapses were found at all parts of filopodia with equal frequency, usually occurring on fusiform swellings of the diameter. Most synaptic contacts (53 ± 11%) occurred directly on dendritic shafts during the first postnatal week. A smaller but still substantial portion (32 ± 12%) of synapses were on shafts at P12 (p< 0.036). There was a highly significant (p< 0.0002) increase in the proportion of dendritic spine synapses with age, rising from just 4.9 ± 4.3% at P1 to 37 ± 14% at P12. The concurrence of primarily shaft and filopodial synapses in the first postnatal week suggests that filopodia recruit shaft synapses that later give rise to spines through a process of outgrowth.
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Filipodia account for roughly 30% of synapses in the mature brain.
“The anatomical substrate for silent synapses is fingerlike dendritic protrusions referred to as filipodia (245), which account for roughly 30% of synapses in the mature brain (240).”
From Synaptic memory and CaMKII (2023) · cites this paper as [245]
The Results (page unavailable) report that filopodial synapses were 21% of identified contacts in developing CA1 during the first postnatal week and fell to 7.2% by postnatal day 12—not roughly 30% in the mature brain. The paper also states that dendritic filopodia disappear as the cortex matures; it does not report a 30% estimate for mature-brain synapses. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThin spines and filopodia may be postsynaptic components of silent synapses.
“In addition, our study suggests that thin spines and filopodia may be postsynaptic components of silent synapses28, 32, 34, 44.”
From Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons (2001) · cites this paper as [44]
The Results report synapses on filopodia, and the Analysis describes how the postsynaptic process was identified as a spine or filopodium. The paper also mentions thin spines, but our copy does not identify synapses on either structure as silent; that qualification is unsupported. (LLM, conf=0.82)
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Cites
Structural abnormalities of the cerebral cortex in human chromosomal aberrations: a Golgi study
Marin-Padilla, M. (1972) · Brain Research · doi:10.1016/0006-8993(72)90324-1 · Cited by 290 · see citing works
The fra(X) syndrome: Neurological, electrophysiological, and neuropathological abnormalities
Wisniewski, K. E., Segan, S. M., Miezejeski, C. M., Sersen, E. A., & Rudelli, R. D. (1991) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320380267 · Cited by 261 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Pappas GD, Fox GQ, Masurovsky EB, Peterson ER, Crain SM (1975) Neuronal growth cone relationships and their role in synaptogenesis in the mammalian central nervous system. In: Advances in Neurology, Vol 12 (Kreutzberg GW, ed), pp 163-180. New York: Raven.
- Purpura DP (1975) Dendritic differentiation in human cerebral cortex: Normal and aberrant development patterns. In: Advances in neurology, Vol 12 (Kreutzberg GW, ed), pp 91-116. New York: Raven.
- Shepherd GMG, Harris K M (1998) Three-dimensional structure and composition of CA3-Ͼ CA1 axons in rat hippocampal slices: implica- tions for presynaptic connectivity and compartmentalization. J Neuro- sci, in press.
Cited by
Sorted by citations
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
Microglial interactions with synapses are modulated by visual experience
Tremblay, M.-È., Lowery, R. L., & Majewska, A. K. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000527 · Cited by 1,542 · see citing works
Long-term dendritic spine stability in the adult cortex
Grutzendler, J., Kasthuri, N., & Gan, W.-B. (2002) · Nature · doi:10.1038/nature01276 · Cited by 1,198 · 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
Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses
Zhou, Q., Homma, K. J., & Poo, M.-M. (2004) · Neuron · doi:10.1016/j.neuron.2004.11.011 · Cited by 1,025 · 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
Dendritic Spine Pathology: Cause or Consequence of Neurological Disorders?
Fiala, J. C., Spacek, J., & Harris, K. M. (2002) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00158-3 · Cited by 811 · see citing works
Self-citationExperience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo
Lendvai, B., Stern, E. A., Chen, B., & Svoboda, K. (2000) · Nature · doi:10.1038/35009107 · Cited by 802 · see citing works
Development of long-term dendritic spine stability in diverse regions of cerebral cortex
Zuo, Y., Lin, A., Chang, P., & Gan, W.-B. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.001 · Cited by 684 · see citing works
Experience-dependent and cell-type-specific spine growth in the neocortex
Holtmaat, A., Wilbrecht, L., Knott, G. W., Welker, E., & Svoboda, K. (2006) · Nature · doi:10.1038/nature04783 · Cited by 631 · see citing works
Synapse formation on neurons born in the adult hippocampus
Toni, N., Teng, E. M., Bushong, E. A., Aimone, J. B., Zhao, C., Consiglio, A., van Praag, H., Martone, M. E., Ellisman, M. H., & Gage, F. H. (2007) · Nature Neuroscience · doi:10.1038/nn1908 · Cited by 579 · see citing works
Miniature synaptic events maintain dendritic spines via AMPA receptor activation
McKinney, R. A., Capogna, M., Dürr, R., Gähwiler, B. H., & Thompson, A. S. M. (1999) · Nature Neuroscience · doi:10.1038/4548 · Cited by 523 · see citing works
Dendritic arbor development and synaptogenesis
Cline, H. T. (2001) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00182-3 · Cited by 499 · see citing works
The Subspine Organization of Actin Fibers Regulates the Structure and Plasticity of Dendritic Spines
Honkura, N., Matsuzaki, M., Noguchi, J., Ellis-Davies, G. C. R., & Kasai, H. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.013 · Cited by 490 · 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
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
Krucker, T., Siggins, G. R., & Halpain, S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.100139797 · Cited by 374 · see citing works
Virus cell-to-cell transmission
Mothes, W., Sherer, N. M., Jin, J., & Zhong, P. (2010) · Journal of Virology · doi:10.1128/jvi.00443-10 · Cited by 353 · see citing works
Bonhoeffer, T., & Yuste, R. (2002) · Neuron · doi:10.1016/s0896-6273(02)00906-6 · Cited by 337 · see citing works
Experience-dependent structural plasticity in the cortex
Fu, M., & Zuo, Y. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.02.001 · Cited by 322 · see citing works
A developmental switch in the signaling cascades for LTP induction
Yasuda, H., Barth, A. L., Stellwagen, D., & Malenka, R. C. (2003) · Nature Neuroscience · doi:10.1038/nn985 · Cited by 325 · see citing works
Delayed Stabilization of Dendritic Spines in Fragile X Mice
Cruz-Martin, A., Crespo, M., & Portera-Cailliau, C. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0577-10.2010 · Cited by 321 · see citing works
Bourne, J. N., & Harris, K. M. (2011) · Hippocampus · doi:10.1002/hipo.20768 · Cited by 318 · see citing works
Self-citationRole of actin cytoskeleton in dendritic spine morphogenesis
Sekino, Y., Kojima, N., & Shirao, T. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.04.029 · Cited by 294 · see citing works
Dendritic spines: from structure to in vivo function
Rochefort, N. L., & Konnerth, A. (2012) · The EMBO Reports · doi:10.1038/embor.2012.102 · Cited by 299 · 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
Hayashi, M. L., Choi, S.-Y., Rao, B. S. S., Jung, H.-Y., Lee, H.-K., Zhang, D., Chattarji, S., Kirkwood, A., & Tonegawa, S. (2004) · Neuron · doi:10.1016/j.neuron.2004.05.003 · Cited by 280 · see citing works
Neurogeometry and potential synaptic connectivity
STEPANYANTS, A., & CHKLOVSKII, D. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.05.006 · Cited by 254 · see citing works
Ontogeny of postsynaptic density proteins at glutamatergic synapses
Petralia, R. S., Sans, N., Wang, Y.-X., & Wenthold, R. J. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.03.013 · Cited by 236 · see citing works
The FXG: a presynaptic fragile X granule expressed in a subset of developing brain circuits
Christie, S. B., Akins, M. R., Schwob, J. E., & Fallon, J. R. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3937-08.2009 · Cited by 208 · see citing works
Shi, Y., & Ethell, I. M. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4091-05.2006 · Cited by 200 · see citing works
Kirov, S. A., Petrak, L. J., Fiala, J. C., & Harris, K. M. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.04.053 · Cited by 172 · see citing works
Self-citationChen, N., & Napoli, J. L. (2008) · The FASEB Journal · doi:10.1096/fj.07-8739com · Cited by 166 · see citing works
Sidhu, H., Dansie, L. E., Hickmott, P. W., Ethell, D. W., & Ethell, I. M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1162-14.2014 · Cited by 155 · see citing works
Kawai, H., Zago, W., & Berg, D. K. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-18-07903.2002 · Cited by 140 · see citing works
Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
Garcia, O., Torres, M., Helguera, P., Coskun, P., & Busciglio, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014200 · Cited by 122 · see citing works
Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders?
Yan, Z., Kim, E., Datta, D., Lewis, D. A., & Soderling, S. H. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2360-16.2016 · Cited by 120 · 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
Distinct Lineage-Dependent Structural and Functional Organization of the Hippocampus
Xu, H.-T., Han, Z., Gao, P., He, S., Li, Z., Shi, W., Kodish, O., Shao, W., Brown, K. N., Huang, K., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.067 · Cited by 80 · see citing works
Djenoune, L., Desban, L., Gomez, J., Sternberg, J. R., Prendergast, A., Langui, D., Quan, F. B., Marnas, H., Auer, T. O., Rio, J.-P., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-00350-1 · Cited by 65 · see citing works
Bell, M. E., Bourne, J. N., Chirillo, M. A., Mendenhall, J. M., Kuwajima, M., & Harris, K. M. (2014) · Journal of Comparative Neurology · doi:10.1002/cne.23646 · Cited by 72 · see citing works
Self-citationKhanal, P., & Hotulainen, P. (2021) · Cells · doi:10.3390/cells10092392 · Cited by 60 · 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
Isochronic development of cortical synapses in primates and mice
Wildenberg, G., Li, H., Sampathkumar, V., Sorokina, A., & Kasthuri, N. (2023) · Nature Communications · doi:10.1038/s41467-023-43088-3 · Cited by 31 · see citing works
Fluorescence imaging of synapse formation and remodeling
Okabe, S. (2013) · Microscopy · doi:10.1093/jmicro/dfs083 · Cited by 26 · see citing works
Zago, W. M., Massey, K. A., & Berg, D. K. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.11.009 · Cited by 24 · see citing works
Time-lapse imaging of dendritic spines in vitro
Verkuyl, J. M., & Matus, A. (2006) · Nature Protocols · doi:10.1038/nprot.2006.357 · Cited by 13 · see citing works
- Authors
- Fiala, J. C., Feinberg, M., Popov, V., & Harris, K. M.
- Affiliations
- Boston Children's Hospital (US)
- Russian Academy of Sciences (RU)
- ORCID
- Harris, Kristen M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-11-01
- Volume
- 18
- Issue
- 21
- Pages
- 8900-8911
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6793554
- OpenAlex
- W2103762808
- Cited by
- 758
- References
- 2
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 13 · 2023: 14 · 2022: 19 · 2021: 22 · 2020: 22 · 2019: 23 · 2018: 16 · 2017: 19 · 2016: 30 · 2015: 29 · 2014: 37 · 2013: 34 · 2012: 36
- FWCI
- 10.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration
- National Institutes of Health (NS21184, NS33574)
- National Institute of Mental Health (R01 MH/DA 57351)
- National Institute on Drug Abuse (R01DA057351)
- National Institute of Neurological Disorders and Stroke (R01NS033574, R01NS021184, NS21184, NS33374, R37NS021184)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dendritic filopodia, synaptogenesis, dendritic spines, hippocampal CA1, excitatory synapses, postnatal development, synaptic connectivity
- MeSH terms
- Aging, Animals, Animals, Newborn, Dendrites, Hippocampus, Image Processing, Computer-Assisted, Male, Microscopy, Electron, Models, Anatomic, Pseudopodia, Synapses, Rats, Long-Evans, Rats
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