The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index; none of the 6 sources its claims cite is checked for support yet.
Dynamic actin filaments are required for stable long-term potentiation (LTP) in area CA1 of the hippocampus
Open accessAbstract
The hypothesis that dynamic actin filaments participate in specific aspects of synaptic plasticity was investigated at the Schaffer-collateral-CA1 pyramidal cell synapse of mouse hippocampus. Low concentrations (0.01–1 μM) of compounds that inhibit actin filament assembly were bath applied to hippocampal slices during extracellular recording of field excitatory postsynaptic potentials. Cytochalasin D, cytochalasin B, and latrunculin A all impaired the maintenance of LTP induced by brief high-frequency stimulation. This effect on LTP maintenance was specific, because none of the compounds affected basal synaptic transmission, paired-pulse facilitation, LTP induction, or post-tetanic potentiation. The effect of cytochalasin B was reversible. The results are consistent with a model in which dynamic actin filaments play an essential role in the molecular mechanisms underlying the early maintenance phase of LTP, such as growth of new synaptic connections or conversion of silent synapses.
Overview
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Written from the paper’s full text.
TL;DR
Low concentrations of actin filament assembly inhibitors selectively impaired maintenance of LTP at Schaffer-collateral–CA1 synapses without affecting basal synaptic transmission, paired-pulse facilitation, LTP induction, or post-tetanic potentiation. The results suggest dynamic actin filaments are required during the early maintenance phase of LTP, possibly for structural remodeling or receptor trafficking.
Key findings
- Cytochalasin D, cytochalasin B, and latrunculin A (0.01–1 μM) did not significantly alter basal pEPSPs, pharmacologically isolated NMDA-pEPSPs, presynaptic fiber volleys, or paired-pulse facilitation over 90 min.
- In untreated slices, LTP was stable at 214 ± 17% of baseline at 100 min and 211 ± 20% at 130 min after tetanus. Pretreatment with actin assembly inhibitors reduced maintained LTP: cytochalasin D reached about 140% of baseline after 60 min, cytochalasin B about 148% at 130 min, and latrunculin A about 139% at 130 min.
- When superfused after LTP induction, cytochalasin D reduced LTP to 165 ± 17% at 100 min and 121 ± 12% at 180 min; cytochalasin B to 182 ± 12% at 100 min and 146 ± 15% at 180 min; latrunculin A to 165 ± 3% at 100 min and 140 ± 12% at 180 min.
- Cytochalasin B effects were at least partially reversible: after washout and a second tetanus, LTP was stable, and 0.01 μM cytochalasin B for 5 min reduced first LTP but allowed robust, nondecremental LTP of about 200% after the second tetanus.
Methods
- Hippocampal slices (400 μm) from normal C57BL/6 male mice (32 ± 0.8 days old) were maintained in oxygenated ACSF at 32 ± 0.2°C.
- Extracellular recordings of presynaptic fiber volleys and population EPSPs were made in stratum radiatum of CA1 with Schaffer-collateral stimulation; input–output curves and paired-pulse facilitation at 20, 50, 100, and 200 ms were tested.
- LTP was induced by two tetani of 100 Hz, 20 sec apart, with responses followed up to 180 min; drugs were bath-applied before or immediately after LTP induction. pEPSP slope, amplitude, and area were analyzed, with Mann–Whitney U tests and P ≤ 0.05 considered significant.
Limitations
- The paper states that the precise time window when dynamic actin filaments participate in LTP maintenance remains to be determined, and the precise nature and location of the essential actin filaments are not identified.
- The authors state their studies do not rule out a role for dynamic actin in other regions of the neuron or in glial cells.
- Evident from the text: experiments used only male C57BL/6 mice at one developmental age, in vitro slices, extracellular field recordings, and small group sizes (e.g., n = 3–7 per condition), which limits generalization and statistical power.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
21 Own result · 8 Own interpretation · 3 Not checked yet · 3 No basis given · 2 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“none of the compounds affected basal synaptic transmission, paired-pulse facilitation, LTP induction, or post-tetanic potentiation.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The presynaptic volley amplitude did not change during the entire recording time, suggesting that there were no modifications of the fiber input (data not shown).”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The presynaptic volley amplitude is proportional to the number of presynaptic neurons recruited by stimulation.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“none of the compounds affected basal synaptic transmission, paired-pulse facilitation, LTP induction, or post-tetanic potentiation.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“none of the compounds affected basal synaptic transmission, paired-pulse facilitation, LTP induction, or post-tetanic potentiation.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, a lower concentration of cytochalasin B (0.01 μM, n = 5) superfused for 5 min also reduced the magnitude of LTP in a manner indistinguishable from the effect of higher concentrations.”
plaindirectn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“none of the compounds affected basal synaptic transmission, paired-pulse facilitation, LTP induction, or post-tetanic potentiation.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Control (untreated) slices exhibited stable LTP of 214 ± 17% of baseline at 100 min and 211 ± 20% at 130 min after tetanus.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, all LTP magnitudes at 100 and 130 min were significantly reduced relative to control (P < 0.012).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Pretreatment with Actin Assembly Inhibitors Impairs LTP.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“slices incubated with cytochalasin D (1 μM, n = 4; 0.1 μM, n = 3; data pooled) showed reduced PTP but were subsequently potentiated to about 200% of baseline after 10 min, then declined steadily to reach a plateau of about 140% of baseline after 60 min of LTP induction.”
plaindirectn = 4- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 13
- Probably not a substantial claim. 6
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 100 min after LTP induction, LTP magnitude was 165 ± 17% of baseline (significantly different from untreated slices, P < 0.015) and further declined to 121 ± 12% of baseline after 180 min.”
plainn = 7 ·- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Like the cytochalasin D effect, after 100 min of LTP induction, cytochalasin B (0.1 μM, n = 3) and latrunculin A (0.1 μM, n = 5) reduced the average pEPSP slope to 182 ± 12% and 165 ± 3% of baseline, respectively. After 180 min, both drugs reduced LTP magnitude significantly (P < 0.02) to 146 ± 15% and 140 ± 12% of baseline, respectively.”
plaindirectn = 5 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Slices incubated with cytochalasin B (0.1 μM, n = 5) also showed reduced PTP, although this was not significant. Responses were potentiated after 10 min to values similar to those in control slices but then declined steadily afterward and reached about 148% of baseline 130 min after tetanus.”
plaindirectn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“slices incubated with latrunculin A (0.1 μM, n = 5) showed nonsignificantly reduced PTP, were potentiated for 10 min, and declined to about 139% of baseline 130 min after tetanus.”
plainn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cytochalasin D, cytochalasin B, and latrunculin A all impaired the maintenance of LTP induced by brief high-frequency stimulation.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, the presynaptic fiber volley and PPF remain unchanged.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The presynaptic volley amplitude is proportional to the number of presynaptic neurons recruited by stimulation.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, we observed robust LTP after the second set of tetani. This enhancement declined only slightly and reached a plateau of about 200% of control after 30 min.”
plainn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our results also suggest that dynamic actin filaments in the presynaptic compartment do not take part in basal synaptic transmission or in short-term plasticity.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The final concentration of DMSO in the slice chamber never exceeded 0.1%, a concentration found in control experiments to have no detectable effects on the slices.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Latrunculins bind to G-actin in a 1:1 molar complex, thereby limiting the availability of actin monomers for polymerizing at either barbed or pointed ends of actin filaments (4).”
What the sources say
- Not checked yetcites [4] Spector I, Shochet N R, Blasberger D, Kashman Y. Cell Motil Cytoskeleton. 1989;13:127–144. doi: 10.1002/cm.970130302. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“These actin inhibitors selectively disrupt filaments undergoing rapid length excursions, leaving intact the more stable and slowly-turning-over actin filaments.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The use of low but effective concentrations of actin inhibitors was designed to avoid nonspecific effects.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, whereas dynamic filaments in dendrites and spines are logical candidates, our studies do not rule out a role for dynamic actin in other regions of the neuron or in glial cells.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because this LTP magnitude resembled normal levels and was nondecremental, this finding suggests that cytochalasin B effects are reversible.”
hedgedconditionaln = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Cytochalasin D exhibits poor washout in intact preparations, whereas cytochalasin B effects are more readily reversible.
None of the sources cited for this claim have been checked yet.
In the paper
“The concentrations of latrunculin A and cytochalasins used here (0.01–1 μM) are similar to those that have been shown previously to alter actin filament organization in cultured cells, prevent lamellipodial ruffling in fibroblasts, inhibit motility and retrograde flow in neuronal growth cones, and arrest dendritic spine motility in hippocampal neurons (3, 4, 7, 10).”
What the sources say
- Not checked yetcites [3] Cooper J A. J Cell Biol. 1987;105:1473–1478. doi: 10.1083/jcb.105.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [4] Spector I, Shochet N R, Blasberger D, Kashman Y. Cell Motil Cytoskeleton. 1989;13:127–144. doi: 10.1002/cm.970130302. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [7] Forscher P, Smith S J. J Cell Biol. 1988;107:1505–1516. doi: 10.1083/jcb.107.4.1505. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [10] Fischer M, Kaech S, Knutti D, Matus A. Neuron. 1998;20:847–854. doi: 10.1016/s0896-6273(00)80467-5. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“at low concentrations, their primary effect in cells is to cap the barbed ends of actin filaments (3).”
What the sources say
- Not checked yetcites [3] Cooper J A. J Cell Biol. 1987;105:1473–1478. doi: 10.1083/jcb.105.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Under the conditions used here, the application of actin perturbing agents is not expected to disrupt stable actin filaments or induce collapse of dendritic spines.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Cytochalasin D exhibits poor washout in intact preparations, whereas cytochalasin B effects are more readily reversible.
“It has been reported that cytochalasin D exhibits poor washout in intact preparations, but that effects of cytochalasin B are more readily reversible.”
The paper relies on this without support.
The presynaptic volley amplitude is proportional to the number of presynaptic neurons recruited by stimulation.
“the amplitude of the presynaptic volley, which is proportional to the number of presynaptic neurons recruited by stimulation”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The expression of AMPA receptors in spines is dependent on F-actin11,17 and scaffolding proteins18,19.”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [11]
Experimental — accuracy not yet measuredIn the citing paper
“Actin polymerization is an essential step of this kind (9, 15–17)”
From Synaptic evidence for the efficacy of spaced learning (2012) · cites this paper as [17]
In the citing paper
“consistent with the previous observation that a low concentration of this agent blocked long-term but not early potentiation11”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [11]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Methods
“To assess drug effects on synaptic efficacy, we generated additional I-O curves at 20 and 40 min after the start of drug superfusion with the same stimulation intensities as those under control conditions.”
§ Results
“After 40 and 80 min of cytochalasin D superfusion, additional I-O curves performed at the same stimulation intensities as under control conditions also showed no detectable changes (Fig. 2A).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Discussion
“In addition, drug wash-out experiments show that the inhibition of LTP by AAIs is reversible.”
§ Results
“Similarly, we observed that, in contrast to the effects of cytochalasin D and latrunculin A, the effects of cytochalasin B on LTP appeared to be at least partially reversible (Fig. 4C).”
Citations
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Metadata
- Authors
- Krucker, T., Siggins, G. R., & Halpain, S.
- Affiliations
- Scripps Research Institute (US)
- ORCID
- Halpain, Shelley
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-05-23
- Volume
- 97
- Issue
- 12
- Pages
- 6856-6861
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC18765
- OpenAlex
- W2041963785
- Semantic Scholar
- 879b8456d922579733d332c78244f89936f74a66
- Cited by
- 374
- References
- 36
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 7 · 2023: 8 · 2022: 1 · 2021: 11 · 2020: 7 · 2019: 5 · 2018: 10 · 2017: 8 · 2016: 10 · 2015: 10 · 2014: 17 · 2013: 23 · 2012: 23
- FWCI
- 6.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH050861, MH47680, P50MH047680)
- National Institute of Neurological Disorders and Stroke (R01NS037311, NS37311)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- F-actin, long-term potentiation, hippocampus, CA1 pyramidal neurons, Schaffer collateral synapses, synaptic plasticity, cytochalasin B, cytochalasin D, latrunculin A, actin filament assembly, silent synapses, field excitatory postsynaptic potentials
- MeSH terms
- Actins, Animals, Cytochalasin B, Hippocampus, Male, Mice, Inbred C57BL, Synaptic Transmission, Neuronal Plasticity, Long-Term Potentiation, Mice
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