Hippocampal LTP Is Accompanied by Enhanced F-Actin Content within the Dendritic Spine that Is Essential for Late LTP Maintenance In Vivo
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The dendritic spine is an important site of neuronal plasticity and contains extremely high levels of cytoskeletal actin. However, the dynamics of the actin cytoskeleton during synaptic plasticity and its in vivo function remain unclear. Here we used an in vivo dentate gyrus LTP model to show that LTP induction is associated with actin cytoskeletal reorganization characterized by a long-lasting increase in F-actin content within dendritic spines. This increase in F-actin content is dependent on NMDA receptor activation and involves the inactivation of actin depolymerizing factor/cofilin. Inhibition of actin polymerization with latrunculin A impaired late phase of LTP without affecting the initial amplitude and early maintenance of LTP. These observations suggest that mechanisms regulating the spine actin cytoskeleton contribute to the persistence of LTP.
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Several other proteins known to signal via actin-regulatory pathways, including VCP/neurofibromin, NESH/Abi-3 and Cofilin, drive similar effects on spine structure when either up- or downregulated.
“As we observe an increase in immature spines upon CYFIP1 overexpression or haploinsufficiency in vitro, it is interesting to note that several other proteins known to signal via actin-regulatory pathways have been shown to drive similar effects on spine structure when either up- or downregulated, including VCP/neurofibromin, NESH/Abi-3 and Cofilin.47,48,57,64, 65, 66, 67”
From The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (2014) · cites this paper as [57]
The Discussion (page unavailable) links ADF/cofilin to actin dynamics and proposes that its phosphorylation may regulate spine morphology. It also reports abnormal spine morphology in LIMK-1 knockout mice, but does not show that up- or downregulating cofilin itself produces the cited increase in immature spines. The other named proteins are not findings attributed specifically to this paper. (LLM, conf=0.82)
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- Authors
- Fukazawa, Y., Saitoh, Y., Ozawa, F., Ohta, Y., Mizuno, K., & Inokuchi, K.
- Affiliations
- National Institute for Physiological Sciences (JP)
- Tottori University (JP)
- Tohoku University (JP)
- Yokohama National University (JP)
- Corresponding author
- Inokuchi, Kaoru
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 38
- Issue
- 3
- Pages
- 447-460
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2040653138
- Cited by
- 695
- References
- 6
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 14 · 2023: 13 · 2022: 17 · 2021: 19 · 2020: 21 · 2019: 20 · 2018: 17 · 2017: 27 · 2016: 36 · 2015: 26 · 2014: 39 · 2013: 39 · 2012: 44
- FWCI
- 14.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3730 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- long-term potentiation, dendritic spines, F-actin, actin cytoskeleton, NMDA receptor, cofilin, actin depolymerizing factor, latrunculin A, dentate gyrus, synaptic plasticity, LTP maintenance
- MeSH terms
- Actins, Animals, Dendrites, Immunohistochemistry, Male, Microfilament Proteins, Microscopy, Electron, Models, Neurological, Synaptic Transmission, Neuropeptides, Synapses, Thiazoles, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Long-Term Potentiation, Dentate Gyrus, Bridged Bicyclo Compounds, Heterocyclic, Actin Depolymerizing Factors, Rats, Thiazolidines
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