The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index; 10 of the 34 sources its claims cite were checked for support.
Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons
Open accessAbstract
Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Using two-photon uncaging of a newly developed caged glutamate, this study mapped functional AMPA receptors on individual dendritic spines of hippocampal CA1 pyramidal neurons. It finds that AMPA receptor expression is tightly correlated with spine-head geometry, with mushroom spines bearing many receptors and thin spines/filopodia few, suggesting independent regulation at single spines.
Key findings
- AMPA-type glutamate receptors are abundant in mushroom spines (up to 150/spine) but sparsely distributed in thin spines and filopodia; thin spines and filopodia may serve as structural substrates of silent synapses.
- Glutamate sensitivity of individual spines correlated strongly with spine-head volume: correlation coefficient r = 0.69–0.90 (0.80 ± 0.07; n = 9) within one dendrite, 0.89 in one example, and 0.77 for the average of 9 dendrites; correlation with spine length was weak and negative (r = 0.30).
- Nonstationary fluctuation analysis estimated 46–147 AMPA receptors in mushroom spines (82 ± 31; mean ± s.d., n = 8), with single-channel currents of 0.4–0.8 pA (0.6 ± 0.1 pA); estimated opening probability was 0.27, suggesting postsynaptic AMPA receptors are not saturated by glutamate from a single vesicle.
- Autocorrelation analysis along dendrites showed no correlation even in neighboring spines for glutamate sensitivities or spine-head volumes, suggesting AMPA receptor expression is controlled independently at the level of individual spines.
Methods
- Two-photon uncaging of MNI-glutamate combined with whole-cell patch-clamp electrophysiology and fluorescence imaging in cultured hippocampal neurons and acute hippocampal slices from rats (cultured neurons from P1 Wistar rats, used at 17–25 days; slices from 15–22 day old Sprague–Dawley rats unless otherwise stated; some young animals 7–9 days old).
- Functional mapping used pseudorandom scanning at 0.33 μm lateral intervals and z-axis sections separated by 0.8 μm, recording 2pEPSCs at −70 mV; spine-head volume was estimated from fluorescence images, and autocorrelation and nonstationary fluctuation analysis (with 0.1 mM cyclothiazide) were used.
- Analysis included kinetic/diffusion modeling of glutamate concentration and AMPA receptor opening, correlation coefficients, coefficients of variation, and estimation of receptor number and single-channel current.
Limitations
- Stated in the paper: the mechanism by which spine-head volume affects AMPA receptor trafficking remains to be determined, and whether thin spines, filopodia, and dendritic shafts transform into thicker spines after long-term potentiation is unknown. Spatial resolution in slices was slightly reduced (0.6 μm laterally and 1.4 μm axially) because of the lower numerical aperture lens, so dendrites with relatively sparse spines (~1 spine/μm) were studied; correlation values were reduced by channel noise (CV ~0.08) and sampling error (CV = 0.1).
- Evident from the text: experiments were performed at room temperature (23–25°C), in cultured neurons or acute slices from juvenile rats, and the main structure–function relationship is correlational rather than causal; some analyses relied on small samples (e.g., n = 7–9 dendrites, n = 8 for fluctuation analysis).
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
10 of 34 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Nevertheless, two-photon excitation of MNI-glutamate permits the functional mapping of glutamate sensitivity with a spatiotemporal resolution similar to that achieved by activation of presynaptic terminals (~0.4μm and ~0.1 ms)28.”
What the sources say
- Could not verifycites [28] Rusakov, D. A. & Kullmann, D. M. Extrasynaptic glutamate diffusion in the hippocampus: ultrastructural constraints, uptake, and receptor activation. J. Neurosci. 18, 3158–3170 (1998). sourceExperimental — accuracy not yet measured
The Synaptic currents and Activation of extrasynaptic receptors sections discuss modeled glutamate diffusion and receptor activation at distances around 400–465 nm; they do not describe the resolution of functional mapping. Searches for MNI-glutamate, two-photon excitation, and the claimed 0.1 ms resolution found no passage addressing the comparison with presynaptic-terminal activation. Page numbers were not available in our copy. (LLM, conf=0.76)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This observation suggests that the expression of AMPA receptors is controlled independently at a level of the individual spine, consistent with the classical notion that a single spine may behave as an independent chemical compartment to regulate synaptic transmission13, 14.”
What the sources say
- Partly supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). sourceExperimental — accuracy not yet measured
The Serial electron microscopy section (p. 2983) proposes that constricted spine necks might limit diffusion to neighboring synapses, supporting the cited notion of a spine as a possible chemical compartment. The discussion of spine geometry and synaptic efficacy (page not specified in our copy) likewise treats compartmentation as a possibility. Neither passage establishes that AMPA-receptor expression is controlled independently at each spine. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [14] Yuste, R. & Denk, W. Dendritic spines as basic functional units of neuronal integration. Nature 375, 682–684 (1995). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition, our study suggests that thin spines and filopodia may be postsynaptic components of silent synapses28, 32, 34, 44.”
What the sources say
- Could not verifycites [28] Rusakov, D. A. & Kullmann, D. M. Extrasynaptic glutamate diffusion in the hippocampus: ultrastructural constraints, uptake, and receptor activation. J. Neurosci. 18, 3158–3170 (1998). sourceExperimental — accuracy not yet measured
The Activation of extrasynaptic receptors section discusses NMDA-receptor activation at neighboring synapses and notes that dendritic spines may change shape, but does not identify thin spines or filopodia as components of silent synapses. Searches for “filopodia,” “thin spines,” and “silent synapses” found no passage making that connection; silent synapses appear in the References. (LLM, conf=0.74)
- Not checked — no full text of the sourcecites [32] Gomperts, S. N., Rao, A., Craig, A. M., Malenka, R. C. & Nicoll, R. A. Postsynaptically silent synapses in single neuron cultures. Neuron 21, 1443–1451 (1998). source
- Not checked — no full text of the sourcecites [34] Durand, G. M., Kovalchuk, Y. & Konnerth, A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71–75 (1996). source
- Partly supportedcites [44] Fiala, J. C., Feinberg, M., Popov, V. & Harris, K. M. Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. J. Neurosci. 18, 8900–8911 (1998). sourceExperimental — accuracy not yet measured
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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Regions of glutamate sensitivity tended to be asymmetrically localized to one portion of a spine (Figs. 3h and 4c–j), consistent with the predominant localization of AMPA receptors within PSDs with a diameter of 0.1 to 0.5μm13, 19, 20.”
What the sources say
- Partly supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). sourceExperimental — accuracy not yet measured
The citation follows the sentence’s PSD explanation, while the asymmetric glutamate-sensitivity observation is presented as the citing paper’s own finding. In “Relationships between hippocampal spine geometry and,” Harris and Stevens describe PSDs as occupying only a small portion of spine surface and suggest that larger PSDs contain more receptors. Our copy does not establish that the receptors are specifically AMPA receptors or give the stated 0.1–0.5 μm PSD diameter. (LLM, conf=0.79)
- Partly supportedcites [19] Nusser, Z. et al. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21, 545–559 (1998). sourceExperimental — accuracy not yet measured
The paper’s Figure 9 caption shows AMPA-receptor labeling at synaptic junctions on spines, supporting the localization invoked to explain the citing authors’ own glutamate-sensitivity observations. It also shows labeling in the spine apparatus and extrasynaptic membrane, and the passages do not establish the stated PSD diameter of 0.1–0.5 μm. The asymmetric glutamate-sensitivity finding is attributed to the citing paper’s figures, not to this source. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [20] Takumi, Y., Ramirez-Leon, V., Laake, P., Rinvik, E. & Ottersen, O.P. Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat. Neurosci. 2, 618–624 (1999). source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The relationship between spine geometry and expression of functional AMPA receptors demonstrated here provides substantial support to the hypothesis that neuronal fine structures have functional correlates in the brain13, 18, 21.”
What the sources say
- Supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). source
In “Serial electron microscopy,” the paper reports that spine-head dimensions correlate with postsynaptic density area and presynaptic vesicle number, and interprets this as evidence that spine-head dimensions reflect synaptic efficacy. That supports the cited hypothesis that neuronal fine structure has functional correlates. The AMPA-receptor relationship is described as demonstrated in the citing paper itself, not attributed to this source; page numbers are not shown for the decisive passages. (LLM, conf=0.90)
- Not matchedcites [18] Cajal, R. y. Histologie du Systeme Nerveux de l'Homme et des Vertebres (Maloine, Paris, 1911).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [21] Segal, M., Korkotian, E. & Murphy, D. D. Dendritic spine formation and pruning: common cellular mechanisms? Trends Neurosci. 23, 53–57 (2000). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
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
“Under physiological conditions, MNI-glutamate was stable for 24 hours, and did not activate any current at a concentration of 10 mM.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“This uncaging regime produced little or no photodamage29, as shown by the stability of the amplitudes of the 2pEPSCs over 1 min (Fig. 1h).”
What the sources say
- Not checked — no full text of the sourcecites [29] Hopt, A. & Neher, E. Highly nonlinear photodamage in two-photon fluorescence microscopy. Biophys. J. 80, 2029–2036 (2001). source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Under physiological conditions, MNI-glutamate was stable for 24 hours, and did not activate any current at a concentration of 10 mM.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 time course of 2pEPSC is well-predicted (smooth line in Fig. 1c) from rapid photolysis (10μs) of MNI-glutamate within a focal volume of two-photon excitation with lateral and axial full-width-at-half-maximal (FWHM) diameter of 0.29 and 0.89μm, respectively (black lines in Fig. f and g; see Methods).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 spatial resolution of glutamate receptor activation was inferred from a small, isolated, glutamate-sensitive region of a dendrite (Fig. 2d), yielding lateral and axial FWHM diameters of 0.45 and 1.1μm, respectively (green lines in Fig. 1f and g).”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 13
- Probably not a substantial claim. 16
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Given that each spine receives only one synaptic input13, our data indicate the highest possible degree of freedom is available in synaptic connections in the dendrites, which has been assumed in the learning models of most neural network theories17.”
What the sources say
- Partly supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [17] Arbib, M. A. The Handbook of Brain Theory and Neural Networks (MIT Press, Cambridge, Massachusetts, 1995). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“These data are consistent with the correlation between AMPA receptor immunoreactivity and the size of PSD19, 20, because the size of PSD is nearly proportional to the spine-head volume13.”
What the sources say
- Supportedcites [19] Nusser, Z. et al. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21, 545–559 (1998). source
Figure 4B and 4D report significant positive correlations between synapse size and AMPA-receptor immunoparticle content in Schaffer collateral and mossy fiber synapses. The separate claim about spine-head volume is attached to citation 13, not to this source. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [20] Takumi, Y., Ramirez-Leon, V., Laake, P., Rinvik, E. & Ottersen, O.P. Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat. Neurosci. 2, 618–624 (1999). source
- Supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). source
The Serial electron microscopy section reports that PSD area is positively correlated with spine volume, much more strongly with spine-head volume than with spine-neck volume. The Discussion describes spine-head dimensions as proportional to PSD area. The AMPA receptor immunoreactivity correlation is attached to other citations, not this source. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
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
“Moreover, it did not affect either the amplitude (Fig. 1b) or the time course (Fig. 1b, inset) of miniature excitatory postsynaptic currents (mEPSCs), indicating that it does not exert an antagonistic effect at AMPA receptors.”
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“We developed a methoxy derivative of nitroindolino-glutamate, MNI-glutamate (Fig. 1a), that possesses a two-photon cross section (0.06 GM; 1 GM = 10−50 cm4s/photon2) sufficiently large for biological application (see Methods).”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Thin spines exhibited little (Fig. 4a and b) or slight glutamate sensitivity (Fig. 4c–e), and thick mushroom spines displayed large sensitivity to uncaged glutamate (Fig. 4f–j).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“The spatial resolution of AMPA-receptor mapping was slightly reduced compared with cultured neurons, 0.6μm laterally and 1.4μm axially, because of the smaller numerical aperture (NA) of the lens used (0.9).”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In young animals (7 to 9 days old), dendrites were decorated only sparsely with spines34, and most of the dendritic shaft was devoid of glutamate sensitivity (Fig. 4l), although marked expression of functional AMPA receptors was already apparent in mushroom spines present (Fig. 4l).”
What the sources say
- Not checked — no full text of the sourcecites [34] Durand, G. M., Kovalchuk, Y. & Konnerth, A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71–75 (1996). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“The glutamate sensitivity of each PSD (as defined by the maximum glutamate sensitivity of a spine) was significantly correlated with the volume of the spine head (Fig. 5a); the correlation coefficient (r) was 0.69–0.90 (0.80 ± 0.07; n = 9) within one dendrite (0.89, Fig. 5b) and 0.77 for average of 9 dendrites (Fig. 5c).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The maximal glutamate sensitivity of a spine reflects the number of functional AMPA receptors in that spine.
In the paper
“The two-photon action cross section of MNI-glutamate was obtained as 0.06 GM at 730 nm, using azid-1 as a standard compound with a known action cross section of 1.0 GM at 730 nm48.”
What the sources say
- Not checked — no full text of the sourcecites [48] Brown, E. B., Shear, J. B., Adams, S. R., Tsien, R. Y. & Webb, W. W. Photolysis of caged calcium in femtoliter volumes using two-photon excitation. Biophys. J. 76, 489–499 (1999). source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 time course of 2pEPSC (Fig. 3bA–C) is similar to spontaneous mEPSCs (Fig. 3bE).”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“We also detected slow NMDA-mediated currents when Mg2+ was removed from the extracellular solution; the distribution of these currents was less heterogeneous than that of AMPA receptors, and most spines expressed NMDA receptors (data not shown).”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“For instance, the peak glutamate concentration at the center of irradiation reaches 0.6 mM focally, at a laser power of 7 mW, MNI-glutamate concentration (CMNI) of 8 mM, the duration of irradiation (td) of 50 μs.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“and those larger than 20 μs predict greater loss of spatial resolution than actually obtained (Fig. 1f)”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The evoked currents had a small coefficient of variation (CV) of 0.08, consistent with the post-synaptic action of glutamate23.”
What the sources say
- Not checked — no full text of the sourcecites [23] Liu, G., Choi, S. & Tsien, R. W. Variability of neurotransmitter concentration and nonsaturation of postsynaptic AMPA receptors at synapses in hippocampal cultures and slices. Neuron 22, 395–409 (1999). source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“In the condition listed above, the peak opening probability was 0.15 and 0.2 for 2pEPSC and mEPSC, respectively.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“This might result from less effective transport of AMPA receptors into thinner spines with smaller volume-to-surface ratios.”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 animal experiments were approved by the animal experiment committee of the National Institute for Physiological Sciences, Japan.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 spine-head volume was estimated by total fluorescence of the spine head in the fluorescence images, which was calibrated using the large spine head whose volume (0.087μm3, spine A in Fig. 3f) could be directly estimated by a FWHM diameter.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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 error due to the sampling intervals was estimated as 0.1 (CV), given the spatial resolution of glutamate mapping as 0.6μm laterally and 1.4μm axially.”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Such a weak correlation may be due to the presence of several spines with long length and small spine-head volume (Fig. 5e).”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“These data conform with the development of AMPA receptor immunoreactivity in CA1 pyramidal neurons35.”
What the sources say
- Not checked — no full text of the sourcecites [35] Petralia, R. S. et al. Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nat. Neurosci. 2, 31–36 (1999). source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 point spread function of the focal volume of two-photon excitation were estimated using a 0.1μm fluorescent beads as 0.29 μm (FWHM) laterally and 0.89 μm axially for the inverted microscope (NA, 1.2), and 0.39μm laterally and 1.28μm axially for the upright microscope (NA, 0.9).”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. 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 access resistance was 70% compensated for the experiments shown in Fig. 1c–g but not for others.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“We estimated the CV of the two-photon excitation to be less than 0.03, by measuring the two-photon excited fluorescence of a polar tracer, Alexa Fluor 594 hydrizide (0.2 mM, Molecular Probes, Eugene, Oregon), applied to slice preparations similarly to MNI-glutamate.”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Using two-photon excitation of a caged-glutamate compound, we showed that the expression of functional AMPA receptors among spines shows a large range (CV, 0.5), varying from the minimal (silent) to those bearing more than 140 AMPA channels, and has a strong correlation with spine-head volume.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“This powerful approach thus allows the optical stimulation of dendritic processes in brain slices at the level of the individual synapse.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The paper relies on this without support.
The maximal glutamate sensitivity of a spine reflects the number of functional AMPA receptors in that spine.
“The glutamate sensitivity of each PSD (as defined by the maximum glutamate sensitivity of a spine) was significantly correlated with the volume of the spine head (Fig. 5a);”
The paper relies on this without support.
In the presence of 0.1 mM cyclothiazide, the opening probability of AMPA receptors is greater than 0.5.
“We added the desensitization inhibitor cyclothiazide (0.1 mM, CTZ) to increase the opening probability of AMPA receptors to greater than 0.5.”
The paper relies on this without support.
The largest mEPSC (~19 pA) likely occurred in the mushroom spines with the largest number of AMPA receptors (N = 147, i = 0.48 pA).
“because the opening probability of the AMPA receptors was estimated as 0.27, given that the largest mEPSC was ~19 pA (n = 222) in our experiments, and that such mEPSC likely occurred in the mushroom spines with largest number of AMPA receptors (N = 147, i = 0.48 pA).”
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
“Spine head size is positively correlated with mEPSC amplitude [65], and the functional loss of NMDA receptors in DG granule cells has been associated with impairments in pattern separation [8].”
From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [65]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Given that large spines have been shown to express AMPA receptors abundantly8”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [8]
In the citing paper
“Two-photon uncaging allows the release of glutamate within a small focal volume8, so that activation of glutamate receptors is limited to a region within ca. 1 μm of the uncaging beam.”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [8]
In the citing paper
“which express a small number of AMPA receptors8.”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [8]
In the citing paper
“Amplitudes of AMPA currents were 1–25 pA, (measured with perforated patch-clamp experiments), which were within the range of miniature excitatory postsynaptic currents8.”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [8]
Citations
Cites
Crank, J. (1956) · CERN Document Server (European Organization for Nuclear Research) · Cited by 18,978
Park, G. S. (1975) · Polymer · doi:10.1016/0032-3861(75)90130-5 · Cited by 15,035
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566
The Handbook of brain theory and neural networks
(1996) · Choice Reviews Online · doi:10.5860/choice.33-4484 · Cited by 3,913
Long-Term Potentiation--A Decade of Progress?
Malenka, R. C., & Nicoll, A. R. A. (1999) · Science · doi:10.1126/science.285.5435.1870 · Cited by 2,729
Xu, C., & Webb, W. W. (1996) · Journal of the Optical Society of America B · doi:10.1364/josab.13.000481 · Cited by 2,198
The Handbook of brain theory and neural networks
(2003) · Choice Reviews Online · doi:10.5860/choice.41-0300 · Cited by 1,540
Dendritic spine changes associated with hippocampal long-term synaptic plasticity
Engert, F., & Bonhoeffer, T. (1999) · Nature · doi:10.1038/19978 · Cited by 1,412
Histologie du Système Nerveux de Lʼhomme et des Vertébrés
MNH, &. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199809000-00011 · Cited by 1,351
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
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–500 of 1,565
Soares, C., Lee, K. F. H., Nassrallah, W., & Béïque, J.-C. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1873-13.2013 · Cited by 80
“Spine volume measurements were calculated using an intensity-based method, as previously described (Matsuzaki et al., 2001; Béïque et al., 2006).”
MethodDendritic Spines Prevent Synaptic Voltage Clamp
Beaulieu-Laroche, L., & Harnett, M. T. (2018) · Neuron · doi:10.1016/j.neuron.2017.11.016 · Cited by 79
“NSFA analyzes the amplitude and variance of synaptic currents to estimate parameters such as the number and unitary conductance of synaptic receptors (Benke et al., 1998; Benke et al., 2001; L€uthi et al., 1999; Matsuzaki et al., 2001; Smith et al., 2003).”
InfluentialGlasgow, S. D., Labrecque, S., Beamish, I. V., Aufmkolk, S., Gibon, J., Han, D. C., Harris, S. N., Dufresne, P., Wiseman, P. W., McKinney, R. A., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.09.028 · Cited by 84
Roller Coaster Scanning reveals spontaneous triggering of dendritic spikes in CA1 interneurons
Katona, G., Kaszás, A., Turi, G. F., Hájos, N., Tamás, G., Vizi, E. S., & Rózsa, B. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009270108 · Cited by 79
Telencephalin Slows Spine Maturation
Matsuno, H., Okabe, S., Mishina, M., Yanagida, T., Mori, K., & Yoshihara, Y. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2651-05.2006 · Cited by 86
“This view is supported by recent reports that the width of spine heads correlates with the synapse efficacy (Matsuzaki et al., 2001; Kasai et al., 2003).”
ResultDendritic Spine Dynamics Regulate the Long-Term Stability of Synaptic Plasticity
O’Donnell, C., Nolan, M. F., & van Rossum, M. C. W. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2520-11.2011 · Cited by 78
“Aiii, Spine size is assumed to be proportional to synaptic strength, in accordance with experimental data (Matsuzaki et al., 2001).”
BackgroundResultInfluentialA family of photoswitchable NMDA receptors
Berlin, S., Szobota, S., Reiner, A., Carroll, E. C., Kienzler, M. A., Guyon, A., Xiao, T., Trauner, D. H., & Isacoff, E. Y. (2016) · eLife · doi:10.7554/elife.12040 · Cited by 87
“…control have been addressed by the advent of caged versions of glutamate, NMDA and the pore blocker MK-801, which can be photo-uncaged in very small volumes at precise times (Huang et al., 2005; Kohl et al., 2011; Matsuzaki et al., 2001; Palma-Cerda et al., 2012; Rodrı́guez-Moreno et al., 2011).”
BackgroundMethodSodium channels amplify spine potentials
Araya, R., Nikolenko, V., Eisenthal, K. B., & Yuste, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705282104 · Cited by 80
Synapse-Specific Regulation of AMPA Receptor Subunit Composition by Activity
Harms, K. J., Tovar, K. R., & Craig, A. M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0302-05.2005 · Cited by 76
Organization of the Arp2/3 Complex in Hippocampal Spines
Rácz, B., & Weinberg, R. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0756-08.2008 · Cited by 84
“…evidence shows that long-term potentiation (LTP) induction protocols lead to spine enlargement (Kopec et al., 2006; Park et al., 2006; Harvey and Svoboda, 2007); moreover, the synapses on these enlarged spines express more AMPA-type glutamate receptors (Matsuzaki et al., 2001; Kasai et al., 2003).”
BackgroundBelov, V. N., Mitronova, G. Y., Bossi, M. L., Boyarskiy, V. P., Hebisch, E., Geisler, C., Kolmakov, K. A., Wurm, C. A., Willig, K. I., & Hell, S. W. (2014) · Chemistry - A European Journal · doi:10.1002/chem.201403316 · Cited by 77
Wavelength-Selective One- and Two-Photon Uncaging of GABA
Amatrudo, J. M., Olson, J. P., Lür, G., Chiu, C. Q., Higley, M. J., & Ellis‐Davies, G. C. R. (2013) · ACS Chemical Neuroscience · doi:10.1021/cn400185r · Cited by 85
Self-citationRemote modulation of neural activities via near-infrared triggered release of biomolecules
Li, W., Luo, R., Lin, X., Jadhav, A., Zhang, Z., Yan, L., Chan, C.-Y., Chen, X., He, J., Chen, C., et al. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.06.041 · Cited by 78
Lebeau, G., Maher-Laporte, M., Topolnik, L., Laurent, C. E., Sossin, W., DesGroseillers, L., & Lacaille, J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01844-07 · Cited by 86
“Moreover, elongated spines and filopodium-like protrusions have been shown to be postsynaptic components of silent synapses (38).”
BackgroundResultControl of dendritic spine morphological and functional plasticity by small GTPases.
Woolfrey, K. M., & Srivastava, D. P. (2016) · Neural Plasticity · doi:10.1155/2016/3025948 · Cited by 76
“For example, large dendritic spines are likely to feature large PSDs and make strong connections, while small dendritic spines are indicative of weak connections and may be highly plastic [16].”
BackgroundFauth, M. J., Wörgötter, F., & Tetzlaff, C. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004031 · Cited by 75
“Inspired by biological weight-volume correlation [14] and the volume-lifetime-dependency [3, 12, 13], we model this probability as a decreasing function of the synaptic weight resulting from the Multi-synaptic Connections and Their Functional Consequences”
Dual-wavelength efficient two-photon photorelease of glycine by π-extended dipolar coumarins
Klausen, M., Dubois, V., Clermont, G., et al. (2019) · Chemical Science · doi:10.1039/c9sc00148d · Cited by 75
The discovery of dendritic spines by Cajal in 1888 and its relevance in the present neuroscience
García-López, P., García‐Marín, V., & Freire, M. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.06.002 · Cited by 83
Chun, S., Bayazitov, I. T., Blundon, J. A., & Zakharenko, S. S. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4500-12.2013 · Cited by 78
“Because TGU releases exogenous glutamate from inactive (caged) glutamate (MNI-glutamate) and thereby bypasses the release of endogenous neurotransmitter from thalamic terminals, this method tests only postsynaptic mechanisms of synaptic transmission and plasticity (Matsuzaki et al., 2001).”
Busetto, G., Higley, M. J., & Sabatini, B. L. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.149336 · Cited by 76
“Similarly, 2PLGU analysis of single hippocampal spines in P15–22 animals demonstrated a tight correlation between AMPAR-current amplitude and spine morphology such that small or thin structures had little sensitivity to glutamate (Matsuzaki et al. 2001).”
BackgroundResultInfluentialLi, Y., & Kim, J. (2015) · Hippocampus · doi:10.1002/hipo.22558 · Cited by 78
Handley, E. E., Pitman, K. A., Dawkins, E., Young, K. M., Clark, R. M., Jiang, T., Turner, B. J., Dickson, T. C., & Blizzard, C. A. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw185 · Cited by 73
“recruitment of AMPA receptors (Matsuzaki et al. 2001; Noguchi et al. 2005) and the polymerisation cycling of actin (Honkura et al.”
BackgroundThe role of spontaneous neurotransmission in synapse and circuit development
Andreae, L. C., & Burrone, J. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24154 · Cited by 79
“Interestingly, work at the Drosophila NMJ utilizing mutants of presynaptic function also suggested that the spontaneous release of glutamate could control postsynaptic glutamate receptor clustering (Saitoe, Schwarz, Umbach, Gundersen, & Kidokoro, 2001), which in mammals is strongly correlated with spine size (Matsuzak…”
Backgroundα-Actinin Anchors PSD-95 at Postsynaptic Sites
Matt, L., Kim, K., Hergarden, A. C., Patriarchi, T., Malik, Z. A., Park, D. K., Chowdhury, D., Buonarati, O. R., Henderson, P. B., Gökçek-Saraç, Ç., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.036 · Cited by 77
Seizure‐induced neurogenesis in the adult brain
Kokaia, M. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07612.x · Cited by 76
“, 2007), which is indicative of strong excitatory synapses (Matsuzaki et al., 2001; Hayashi & Majewska, 2005).”
BackgroundO’Leary, O. F., Wu, X., & Ċastrén, E. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.09.015 · Cited by 75
Morrison, J., Wan, P., Corrie, J. E. T., et al. (2002) · Photochemical & Photobiological Sciences · doi:10.1039/b206155d · Cited by 74
Specht, A., Thomann, J., Alarcon, K., et al. (2006) · ChemBioChem · doi:10.1002/cbic.200600111 · Cited by 74
Medalla, M., & Luebke, J. I. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3426-14.2015 · Cited by 72
“Glutamate uncaging experiments have demonstrated that large mushroom spines have the largest EPSC responses of any spine subtype (Matsuzaki et al., 2001).”
BackgroundInfluentialTwo-Photon Uncaging of Glutamate
Ellis‐Davies, G. C. R. (2019) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2018.00048 · Cited by 82
“Spine LTP Is Local and Non-compartmentalized The initial single spine studies by Kasai suggested spines were functionally isolated compartments (Matsuzaki et al., 2001).”
BackgroundMethodInfluentialSelf-citationBell, 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
“After the induction of LTP, spine size, total PSD area, and number of AMPARs are known to increase (Bourne and Harris, 2011; Hering and Sheng, 2001; Lang et al., 2004; Luscher et al., 2000; Matsuzaki et al., 2001; Matsuzaki et al., 2004; Nagerl et al., 2004).”
BackgroundTransient ECM protease activity promotes synaptic plasticity
Magnowska, M., Górkiewicz, T., Beroun, A., Wawrzyniak, M., Rutkowska-Włodarczyk, I., Kaczmarek, L., & Włodarczyk, J. (2016) · Scientific Reports · doi:10.1038/srep27757 · Cited by 75
Medendorp, W. E., Petersen, E. D., Pal, A., Wagner, L., Myers, A. R., Hochgeschwender, U., & Jenrow, K. A. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00087 · Cited by 77
Local Efficacy of Glutamate Uptake Decreases with Synapse Size
Herde, M. K., Bohmbach, K., Domingos, C., Vana, N., Komorowska‐Müller, J. A., Passlick, S., Schwarz, I., Jackson, C. J., Dietrich, D., Schwarz, M. K., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108182 · Cited by 71
Photoactivatable CaMKII induces synaptic plasticity in single synapses
Shibata, A. C. E., Ueda, H. H., Eto, K., Onda, M., Sato, A., Ohba, T., Nabekura, J., & Murakoshi, H. (2021) · Nature Communications · doi:10.1038/s41467-021-21025-6 · Cited by 74
Vanderplow, A. M., Eagle, A. L., Kermath, B. A., Bjornson, K. J., Robison, A. J., & Cahill, M. E. (2021) · Neuron · doi:10.1016/j.neuron.2021.03.008 · Cited by 74
Signalling pathways underlying structural plasticity of dendritic spines
Patterson, M., & Yasuda, R. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01328.x · Cited by 76
“These studies reveal the signalling pathways relaying Ca2+ to the functional and structural plasticity of dendritic spines.”
InfluentialCHMP2B mutants linked to frontotemporal dementia impair maturation of dendritic spines
Belly, A., Bodon, G., Blot, B., Bouron, A., Sadoul, R., & Goldberg, Y. (2010) · Journal of Cell Science · doi:10.1242/jcs.068817 · Cited by 82
“…was not observed in neurones that overexpressed CHMP2B . wt In view of the known correlation between spine head size and amplitude of AMPA receptor-mediated synaptic currents ( ), these data are consistent with the morphologically Matsuzaki et al., 2001 observed reduction in mushroom spines.”
Electrical Advantages of Dendritic Spines
Gulledge, A. T., Carnevale, N. T., & Stuart, G. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036007 · Cited by 80
“Indeed, spine morphology is dynamic [62,63] and correlated with synaptic efficacy: larger synaptic conductances are associated with spines with larger heads, greater AMPA receptor expression, and shorter and wider spine necks [43,45,64–67].”
BackgroundRah, J., Bas, E., Colonell, J. I., Mishchenko, Y., Karsh, B., Fetter, R. D., Myers, E. W., Chklovskii, D. B., Svoboda, K., Harris, T. D., et al. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00177 · Cited by 74
“Furthermore, it is likely that the undetected (false negative) synapses are small in size and therefore likely to be functionally less relevant (Matsuzaki et al., 2001; Murthy et al., 2001).”
BackgroundNakayama, K., Ohashi, R., Shinoda, Y., Yamazaki, M., Abe, M., Fujikawa, A., Shigenobu, S., Futatsugi, A., Noda, M., Mikoshiba, K., et al. (2017) · eLife · doi:10.7554/elife.29677 · Cited by 73
“The mechanism of the EPSP limitation is likely coupled with spine size reduction because spine size is tightly correlated with AMPAR expression level in the spine (Kopec et al., 2007; Matsuzaki et al., 2001).”
BackgroundA role for synaptopodin and the spine apparatus in hippocampal synaptic plasticity
Deller, T., Orth, C. B., Turco, D. D., Vlachos, A., Burbach, G. J., Drakew, A., Chabanis, S., Körte, M., Schwegler, H., Haas, C. A., et al. (2006) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2006.06.013 · Cited by 71
“Interestingly, and in line with our observations, these earlier studies (Spacek and Harris, 1997) showed that the spine apparatus is present only in a subpopulation of spines, predominantly the large and mushroom-shaped variant, that are functionally the most active (Harris and Stevens, 1989; Matsuzaki et al., 2001; N…”
Knafo, S., Venero, C., Merino‐Serrais, P., Fernaud-Espinosa, I., González‐Soriano, J., Ferrer, I., Santpere, G., & DeFelipe, J. (2009) · The Journal of Pathology · doi:10.1002/path.2565 · Cited by 80
“Large spines are also enriched with AMPA receptors [66], which make their synapses functionally stronger [66–68], and they are also needed for synaptic plasticity [69].”
BackgroundInteractive effects of age and estrogen on cortical neurons: implications for cognitive aging
Bailey, M. E., Wang, A. C. J., Hao, J., Janssen, W. G. M., Hara, Y., Dumitriu, D., Hof, P. R., & Morrison, J. H. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.05.045 · Cited by 62
“, 1992), with large numbers of AMPA recepors (Matsuzaki et al., 2001).”
Modulation of dendritic spines in epilepsy: Cellular mechanisms and functional implications
Wong, M. (2005) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2005.08.007 · Cited by 74
Obi-Nagata, K., Temma, Y., & Hayashi‐Takagi, A. (2019) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.95.014 · Cited by 72
Useful Caged Compounds for Cell Physiology
Ellis‐Davies, G. C. R. (2020) · Accounts of Chemical Research · doi:10.1021/acs.accounts.0c00292 · Cited by 72
Self-citationStacho, M., & Manahan‐Vaughan, D. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.806356 · Cited by 77
Santucci, D. M., & Raghavachari, S. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000208 · Cited by 73
“Two-photon glutamate uncaging [17,60,61] or calcium imaging [17,26] can be used to record synaptic activity at single dendritic spines.”
BackgroundConti, R., & Lisman, J. (2003) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0630290100 · Cited by 77
Campos, V., Prado-Alcalá, R. A., León-Jacinto, U., Aguilar-Vázquez, A. R., Quirarte, G. L., Ramı́rez-Amaya, V., & Díaz-Cintra, S. Y. (2010) · Brain Research · doi:10.1016/j.brainres.2010.10.105 · Cited by 70
“This allows them to change their efficiency by modifying the number of AMPA receptors (Ashby et al., 2006; Matsuzaki et al., 2001).”
Rho Signaling in Synaptic Plasticity, Memory, and Brain Disorders
Zhang, H., Zablah, Y. B., Zhang, H., & Jia, Z. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.729076 · Cited by 70
Neurotrophin and Wnt signaling cooperatively regulate dendritic spine formation
Hiester, B. G., Galati, D. F., Salinas, P. C., & Jones, K. R. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2013.04.006 · Cited by 70
“Previous work has established that there is a correlation between dendritic spine size and synaptic strength (Matsuzaki et al., 2001; Zito et al., 2009), and studies have shown that blocking Wnt signaling impairs excitatory neurotransmission (Cerpa et al., 2011; Varela-Nallar et al., 2010).”
Young, M. E., Ohm, D. T., Dumitriu, D., Rapp, P. R., & Morrison, J. H. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.05.008 · Cited by 70
“Spine size and shape have been linked to synaptic plasticity, spine stability, learning, and memory, particularly with respect to mushroom and thin spines (Matsuzaki et al., 2001; Grutzendler et al., 2002; Trachtenberg et al., 2002; Kasai et al., 2003, 2010a,b; Zuo et al., 2005; Holtmaat et al., 2006; Bourne and Harri…”
BackgroundInfluentialMao, W., Watanabe, T., Cho, S., Frost, J. L., Truong, T., Zhao, X., & Futai, K. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.12877 · Cited by 59
“Shank proteins are targeted to postsynaptic sites in spiny neurons and regulate spine size, which determines the number of AMPA receptors on the synapses (Naisbitt et al., 1999; Matsuzaki et al., 2001).”
BackgroundQiu, S., Lu, Z., & Levitt, P. R. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2580-14.2014 · Cited by 81
“Dendritic spine volume and geometry are correlated with glutamate receptor content and functional maturity (Matsuzaki et al., 2001; Nimchinsky et al., 2002) and is implicated in neuropsychiatric conditions (Hutsler and Zhang, 2010; Penzes et al.”
BackgroundOptical switches and triggers for the manipulation of ion channels and pores
Gorostiza, P., & Isacoff, E. Y. (2007) · Molecular BioSystems · doi:10.1039/b710287a · Cited by 68
Morphological changes in dendritic spines of Purkinje cells associated with motor learning
Lee, K., Jung, J., Arii, T., Imoto, K., & Rhyu, I. J. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.06.001 · Cited by 69
“To support this idea, recent work revealed that different spine shapes are associated with differences in synaptic strength, AMPA receptor content, and spine stability (turnover rates) (Holtmaat et al., 2005; Matsuzaki et al., 2001; Xie, Huganir, & Penzes, 2005).”
ResultAttenuation of Synaptic Potentials in Dendritic Spines
Kwon, T., Sakamoto, M., Peterka, D. S., & Yuste, R. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.012 · Cited by 69
“To mimic single-spine EPSPs, we uncaged glutamate to generate uncaging EPSPs (uEPSP) (Araya et al., 2006; Matsuzaki et al., 2001).”
A two-photon and second-harmonic microscope
Nikolenko, V., Nemet, B. A., & Yuste, R. (2003) · Methods · doi:10.1016/s1046-2023(03)00003-3 · Cited by 69
“These improvements of two-photon excitation over conventional fluorescence microscopy have proven to be of great practical advantages: two-photon microscopy have enable, among other things, physiological analysis of dendritic spines [5, 6] and direct functional mapping of synaptic receptors [7] or channels [8] on livi…”
BackgroundPatriarchi, T., Buonarati, O. R., & Hell, J. W. (2018) · The EMBO Journal · doi:10.15252/embj.201899771 · Cited by 68
“Spine size is also well correlated with postsynaptic response strength as determined by glutamate uncaging (Matsuzaki et al, 2001; Asrican et al, 2007; Araya et al, 2014).”
Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy
Ma, Y., Ramachandran, A. K., Ford, N., Parada, I., & Prince, D. A. (2013) · Epilepsia · doi:10.1111/epi.12195 · Cited by 68
Woolfrey, K. M., Sanderson, J. L., & Dell’Acqua, M. L. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2243-14.2015 · Cited by 69
“LTP is usually also associated with the enlargement of dendritic spines (Matsuzaki et al., 2001; Okamoto et al., 2004; Kopec et al., 2006), and we previously found that the AKAP79CS mutant prevented cLTP-induced spine enlargement in cultured neurons (Keith et al.”
BackgroundRobertson, H. R., Gibson, E. S., Benke, T. A., & Dell’Acqua, M. L. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.6093-08.2009 · Cited by 70
“…neurons As mentioned previously, normal postsynaptic development involves recruitment of F-actin and AMPARs to excitatory synapses containing NMDARs, leading to maturation of dendritic spines and increased synaptic strength (Matus, 2000; Matsuzaki et al., 2001; Lamprecht and LeDoux, 2004).”
BackgroundStriatal spine plasticity in Parkinson's disease: pathological or not?
Smith, Y., Villalba, R. M., & Raju, D. V. (2009) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(09)70805-3 · Cited by 72
“This is, indeed, the case in hippocampal pyramidal neurons where large ‘mushroom’ spines express a larger number of AMPA receptors than thin spines and filopodia, indicating that the distribution of functional AMPA receptors is tightly correlated with spine geometry [37].”
Afroz, S., Parato, J., Shen, H., & Smith, S. S. (2016) · eLife · doi:10.7554/elife.15106 · Cited by 70
“…different functions: Thin spines express abundant numbers of NMDARs, are highly motile and plastic (Kasai et al., 2003; Holtmaat et al., 2006), while the larger mushroom spines are relatively more stable and express AMPA receptors predominantly (Dumitriu et al., 2010; Matsuzaki et al., 2001).”
BackgroundHsu, A., Luebke, J. I., & Medalla, M. (2017) · Journal of Comparative Neurology · doi:10.1002/cne.24196 · Cited by 68
“SER, and the proportion and surface area of perforated PSD are some of the many interacting structural variables that determine synaptic efficacy (Baude, Nusser, Molnar, McIlhinney, & Somogyi, 1995; Germuska et al., 2006; Li et al., 2005; Matsuzaki et al., 2001; Murthy, Schikorski, Stevens, & Zhu, 2001; Murthy, Sejnow…”
BackgroundCalì, C., Wawrzyniak, M., Becker, C., Maco, B., Cantoni, M., Jorstad, A., Nigro, B., Grillo, F. W., Paola, V. D., Fua, P., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0198131 · Cited by 68
Distinct synaptic plasticity rules operate across dendritic compartments in vivo during learning
Wright, W. J., Hedrick, N. G., & Komiyama, T. (2025) · Science · doi:10.1126/science.ads4706 · Cited by 73
Photocontrol of Neural Activity: Biophysical Mechanisms and Performance in Vivo
Sjulson, L., & Miesenböck, G. (2008) · Chemical Reviews · doi:10.1021/cr078221b · Cited by 69
Portera‐Cailliau, C. (2011) · The Neuroscientist · doi:10.1177/1073858410395322 · Cited by 72
Presynaptic Gating of Postsynaptically Expressed Plasticity at Mature Thalamocortical Synapses
Blundon, J. A., Bayazitov, I. T., & Zakharenko, S. S. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3281-11.2011 · Cited by 69
“Because TGU releases exogenous glutamate and thereby bypasses the release of endogenous neurotransmitter from presynaptic terminals, this method tests for only postsynaptic mechanisms of synaptic function (Matsuzaki et al., 2001).”
MethodDynamin-dependent Membrane Drift Recruits AMPA Receptors to Dendritic Spines
Jaskolski, F., Mayo-Martin, M. B., Jane, D. E., & Henley, J. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808401200 · Cited by 65
Casting a net on dendritic spines: The extracellular matrix and its receptors
Dansie, L. E., & Ethell, I. M. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20963 · Cited by 68
“Several studies demonstrated a direct correlation between the size of the PSD and the number of glutamate receptors that the spine accommodates (Matsuzaki et al., 2001; Shinohara and Hirase, 2009).”
BackgroundInfluentialWijetunge, L. S., Angibaud, J., Frick, A., Kind, P. C., & Nägerl, U. V. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.5302-13.2014 · Cited by 72
“…morphology Spine morphology is intimately related to synapse function, as spine head size correlates with synaptic strength (Nusser et al., 1998; Matsuzaki et al., 2001) and undergoes changes during synaptic plasticity (Lang et al., 2004; Matsuzaki et al., 2004; Nägerl et al., 2004; Oh et al.,…”
Miwa, H., Fukaya, M., Watabe, A. M., Watanabe, M., & Manabe, T. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.147652 · Cited by 66
“2005), and LTP is easier to induce in smaller spines (Matsuzaki et al. 2001).”
BackgroundAMPA receptor trafficking and LTP: Carboxy-termini, amino-termini and TARPs
Díaz-Alonso, J., & Nicoll, R. A. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108710 · Cited by 66
“, 2021) and the number of receptors (Chen et al., 2015; Matsuzaki et al., 2001; Takumi et al., 1999).”
BackgroundHu, Z., Zhao, J. W., Hu, T., Luo, Y., Zhu, J., & Li, Z. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201404092 · Cited by 65
“All animal procedures followed the National Institutes of Health guideline Using Animals in Intramural Research and were approved by the National Institutes of Mental Health Animal Care and Use Committee.”
Shen, H., Sesack, S. R., Toda, S., & Kalivas, P. W. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0184-2 · Cited by 64
Unified pre- and postsynaptic long-term plasticity enables reliable and flexible learning
Costa, R. P., Froemke, R. C., Sjöström, P. J., & van Rossum, M. C. W. (2015) · eLife · doi:10.7554/elife.09457 · Cited by 67
“As 105 synaptic structure and synaptic weight are closely correlated [32, 33], the memory savings mediated by 106 structural spine plasticity [30] are reminiscent of those provided by our unified plasticity model.”
BackgroundSantuy, A., Rodríguez, J., DeFelipe, J., & Merchán-Pérez, Á. (2018) · eNeuro · doi:10.1523/eneuro.0377-17.2017 · Cited by 66
“Moreover, the EPSP amplitude strongly correlates with the number of postsynaptic AMPA receptors and with spine head volume (Matsuzaki et al., 2001; Kasai et al., 2003; Araya, 2014), which in turn strongly correlates with PSD size (Arellano et al., 2007).”
BackgroundMatsuzaki, M., Ellis‐Davies, G. C. R., & Kasai, H. (2008) · Journal of Neurophysiology · doi:10.1152/jn.01127.2007 · Cited by 64
Self-citationBinary and analog variation of synapses between cortical pyramidal neurons
Dorkenwald, S., Turner, N. L., Macrina, T., Lee, K., Lu, R., Wu, J., Bodor, A. L., Bleckert, A. A., Brittain, D., Kemnitz, N., et al. (2019) · doi:10.1101/2019.12.29.890319 · Cited by 130
“Spine dynamics were interpreted as synaptic plasticity, because spine volume is well-correlated with physiological strength of a synapse (Matsuzaki et al., 2001; Noguchi et al., 2011; Holler-Rickauer, Koestinger and Martin, 2019).”
BackgroundMechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders
Irollo, E., Luchetta, J., Ho, C.-T., Nash, B., & Meucci, O. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03785-y · Cited by 66
“Their large head contains multiple AMPA and NMDA receptors, and their narrow neck provides a well-controlled biochemical microenvironment [77].”
BackgroundOkubo-Suzuki, R., Okada, D., Sekiguchi, M., & Inokuchi, K. (2008) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2008.03.001 · Cited by 64
Activity of the AMPA receptor regulates drebrin stabilization in dendritic spine morphogenesis
Takahashi, H., Yamazaki, H., Hanamura, K., Sekino, Y., & Shirao, T. (2009) · Journal of Cell Science · doi:10.1242/jcs.043729 · Cited by 63
“A typical case of a synaptically functional spine is represented by a mushroom-shaped protrusion possessing a bulbous head and narrow neck (Matsuzaki et al., 2001; Noguchi et al., 2005).”
BackgroundDynamic distribution of endoplasmic reticulum in hippocampal neuron dendritic spines
Toresson, H., & Grant, S. G. N. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04342.x · Cited by 64
“, 1992) and large spines were seen to induce greater glutamate-induced currents than small spines (Matsuzaki et al., 2001).”
BackgroundLavoie‐Cardinal, F., Salesse, C., Bergeron, É., Michel Meunier, A., & Koninck, P. D. (2016) · Scientific Reports · doi:10.1038/srep20619 · Cited by 65
Protein Crowding within the Postsynaptic Density Can Impede the Escape of Membrane Proteins
Li, T. P., Song, Y., MacGillavry, H. D., Blanpied, T. A., & Raghavachari, S. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3154-15.2016 · Cited by 64
van Duinen, M. A., Sambeth, A., Heckman, P. R. A., de Smit, S., Tsai, M., Lahu, G., Uz, T., Blokland, A., & Prickaerts, J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.12.019 · Cited by 63
“The described spine enlargement was associated with an increase in AMPA-receptor-mediated currents (Matsuzaki et al., 2001).”
BackgroundHalbach, O. V. B. U., Krause, S., Medina, D. L., Sciarretta, C., Minichiello, L., & Unsicker, K. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.08.025 · Cited by 63
Momiyama, A., Silver, R. A., Häusser, M., Notomi, T., Wu, Y., Shigemoto, R., & Cull-Candy, S. G. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.033472 · Cited by 65
“…structural properties, it would clearly be of interest to examine these parameters specifically at a single postsynaptic site in response to a known concentration of agonist (for example, by means of two-photon laser uncaging of 4-methoxy-7-nitroindolinylcaged L-glutamate; Matsuzaki et al. 2001).”
BackgroundSrinivas, K. V., Buss, E. W., Sun, Q., Santoro, B., Takahashi, H., Nicholson, D. A., & Siegelbaum, S. A. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2219-16.2017 · Cited by 69
“We also performed a more detailed analysis of spine size because synaptic AMPAR number and, hence, synaptic strength often varies with spine size (e.g., Matsuzaki et al., 2001; Katz et al., 2009).”
MethodSelf-organized reactivation maintains and reinforces memories despite synaptic turnover
Fauth, M. J., & van Rossum, M. C. W. (2019) · eLife · doi:10.7554/elife.43717 · Cited by 60
SpineJ : A software tool for quantitative analysis of nanoscale spine morphology
Levet, F., Tønnesen, J., Nägerl, U. V., & Sibarita, J. (2019) · Methods · doi:10.1016/j.ymeth.2020.01.020 · Cited by 58
Ito, K., Hirooka, Y., Kishi, T., Kimura, Y., Kaibuchi, K., Shimokawa, H., & Takeshita, A. (2004) · Hypertension · doi:10.1161/01.hyp.0000114602.82140.a4 · Cited by 63
Ito, A., Miyazaki, T., Miura, E., Matsuda, K., Watanabe, M., Yuzaki, M., & Okabe, S. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.027 · Cited by 64
“To clarify physiological functions of spine encapsulation, further studies at the single spine level are warranted (Matsuzaki et al., 2001).”
Membrane-initiated estradiol actions mediate structural plasticity and reproduction
Micevych, P. E., & Christensen, A. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.07.003 · Cited by 62
“The stabilization involves receptors being recruited into the spine membrane and anchored at the postsynaptic specialization by scaffold proteins [56, 61, 82, 165].”
BackgroundSynthesis of a caged glutamate for efficient one- and two-photon photorelease on living cells
Fedoryak, O. D., Sul, J., Haydon, P. G., & Ellis‐Davies, G. C. R. (2005) · Chemical Communications · doi:10.1039/b504922a · Cited by 62
Self-citationKalinowska, M., Chávez, A. E., Lutzu, S., Castillo, P. E., Bukauskas, F. F., & Francesconi, A. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.640136 · Cited by 61
“8D), consistent with an overabundance of immature protrusions in these neurons (49).”
Background
Metadata
- Authors
- Matsuzaki, M., Ellis-Davies, G. C. R., Nemoto, T., Miyashita, Y., Iino, M., & Kasai, H.
- Affiliations
- National Institute for Physiological Sciences (JP)
- The University of Tokyo (JP)
- Corresponding author
- Kasai, Haruo
- Venue
- Nature Neuroscience
- Published
- 2001-10-22
- Volume
- 4
- Issue
- 11
- Pages
- 1086-1092
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4229049
- OpenAlex
- W1798313689
- Semantic Scholar
- 0791a25208e00590f1e05aade330dddd88a94dc4
- Cited by
- 1,563
- References
- 53
- Citations by year
- 2026: 30 · 2025: 49 · 2024: 45 · 2023: 70 · 2022: 64 · 2021: 90 · 2020: 71 · 2019: 76 · 2018: 75 · 2017: 65 · 2016: 78 · 2015: 84 · 2014: 75 · 2013: 75 · 2012: 81
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM 53395, R01 GM053395)
- 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
- dendritic spines, AMPA receptors, spine geometry, mushroom spines, filopodia, silent synapses, CA1 pyramidal neurons, hippocampus, glutamate uncaging, excitatory synapses, synaptic plasticity
- MeSH terms
- Animals, Cells, Cultured, Dendrites, Electrophysiology, Glutamates, Hippocampus, Indoles, Mathematics, Microscopy, Fluorescence, Photolysis, Molecular Structure, Rats, Wistar, Pyramidal Cells, Receptors, AMPA, Patch-Clamp Techniques, Glutamic Acid, Excitatory Postsynaptic Potentials, Cell Surface Extensions, Rats, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-12, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-12 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
