Barriers in the brain: resolving dendritic spine morphology and compartmentalization

Probably not a substantial claim: may not pass S3 (load-bearing).

The first STED images of spines in organotypical slices expressing yellow fluorescent protein (YFP) in a sparse subset of neurons were published in 2008.

“The first STED images of spines in organotypical slices expressing yellow fluorescent protein (YFP) in a sparse subset of neurons were published in 2008 (Nägerl et al., 2008).”

• cites Nägerl et al., 2008 sourceSupported

May combine two claims.

Two-photon STED has been successfully applied to dendritic spines in organotypical slices, resulting in 60-150 nm lateral resolution at 50-100 μm depths, but without improving the axial resolution.

“Nevertheless, it has been successfully applied to dendritic spines in organotypical slices, resulting in 60–150 nm lateral resolution at 50–100 μm depths, but without improving the axial resolution (Ding et al., 2009; Bethge et al., 2013; Takasaki et al., 2013).”

• cites Ding et al., 2009 sourcePartly supported

  The Results ('Live-cell imaging of neuron dendrites and spines') report improved imaging of dendritic spines 30–110 μm below the surface, and 'Improved analysis of spine morphology' says lateral, but not axial, resolution improved. However, the experiments used acute mouse brain slices, not organotypic slices. The reported measurements also do not establish the claimed 60–150 nm lateral-resolution range; the Results report a 280 nm FWHM for imaged beads and thin filopodia. (LLM, conf=0.89)

  Experimental — accuracy not yet measured
• cites Bethge et al., 2013 sourceNot checked — no full text of the source
• cites Takasaki et al., 2013 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Modeling studies have often emphasized the interesting effects that shape can have on the diffusion of proteins, calcium ions and other signaling molecules.

“Nevertheless, modeling studies have often emphasized the interesting effects that shape can have on the diffusion of proteins, calcium ions and other signaling molecules (Holcman and Schuss, 2011).”

• cites Holcman and Schuss, 2011 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

SMLM uses switchable fluorophores or special imaging conditions to ensure that only a small, random subset of fluorophores in the sample is emitting at any given time.

“Another set of powerful techniques to achieve resolutions beyond the diffraction barrier uses switchable fluorophores or special imaging conditions to ensure that only a small, random subset of fluorophores in the sample is emitting at any given time (Huang et al., 2009).”

• cites Huang et al., 2009 sourceSupported

May combine two claims.

Calcium ions play a crucial role in initiating downstream signaling during long-term potentiation (LTP) and depression (LTD) and influx of calcium is both necessary and sufficient for structural synaptic plasticity.

“Calcium ions play a crucial role in initiating downstream signaling during long-term potentiation (LTP) and depression (LTD) and influx of calcium is both necessary and sufficient for structural synaptic plasticity (Pettit et al., 1994; Lledo et al., 1995; Otmakhov et al., 2004).”

• cites Pettit et al., 1994 sourceNot checked — no full text of the source
• cites Lledo et al., 1995 sourceNot checked — no full text of the source
• cites Otmakhov et al., 2004 sourcePartly supported

  The Introduction (page unavailable) says Ca²⁺ entry through NMDA channels initiates LTP and activates CaMKII, supporting the LTP signaling portion. The paper also reports spine enlargement after chemical LTP, but it does not establish that calcium influx is both necessary and sufficient for structural synaptic plasticity or address calcium signaling during LTD. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Live super-resolution microscopy requires some thoughtful compromises between temporal and spatial resolution.

“In all cases, live super-resolution microscopy requires some thoughtful compromises between temporal and spatial resolution (Frost et al., 2012).”

• cites Frost et al., 2012 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

During spine enlargement, rapid actin polymerization provides the mechanical force required for pushing out the spine membrane.

“For example, during spine enlargement, rapid actin polymerization provides the mechanical force required for pushing out the spine membrane (Bosch and Hayashi, 2012).”

• cites Bosch and Hayashi, 2012 sourcePartly supported

  In “F-actin regulation as a mechanism underlying structural plasticity” (page not supplied), the paper reports rapid actin polymerization during LTP and proposes that polymerization generates the force enlarging the spine. The citing sentence presents that proposed mechanism as an established fact; the passage does not explicitly describe pushing out the membrane. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Changes in spine size are thought to be generally correlated with changes in the strength of the excitatory synapse.

“Changes in spine size are thought to be generally correlated with changes in the strength of the excitatory synapse (Schikorski and Stevens, 1999; Arellano et al., 2007).”

• cites Schikorski and Stevens, 1999 sourceNot checked — no full text of the source
• cites Arellano et al., 2007 sourceSupported

May combine two claims.

Both Cdc42 and Rho showed a rapid activity peak 30 s after stimulation followed by decay over 5 min and a sustained lower activity for more than 30 min.

“Both Cdc42 and Rho showed a rapid activity peak 30 s after stimulation followed by decay over 5 min and a sustained lower activity for more than 30 min.”

• cites Murakoshi et al., 2011 sourceSupported

May combine two claims.

Rho inactivated five times slower than Cdc42 and could therefore spread into the dendrite.

“In contrast, Rho inactivated five times slower and could therefore spread into the dendrite.”

• cites Murakoshi et al., 2011 sourceSupported

May combine two claims.

Upon single-spine glutamate uncaging, the activation of CaMKII peaked within 6 s and only lasted for a few minutes.

“Upon single-spine glutamate uncaging, the activation of CaMKII peaked within 6 s and only lasted for a few minutes (Lee et al., 2009).”

• cites Lee et al., 2009 sourceSupported

May combine two claims.

Classes of voltage gated calcium channels exclusively localize to spines but not dendrites and cooperate with other calcium channels to shape local depolarization and synaptic plasticity.

“Such an effect is strengthened by the existence of classes of voltage gated calcium channels that exclusively localize to spines but not dendrites and cooperate with other calcium channels to shape local depolarization and synaptic plasticity (Bloodgood and Sabatini, 2007b; Bloodgood et al., 2009).”

• cites Bloodgood and Sabatini, 2007b sourceNot checked — no full text of the source
• cites Bloodgood et al., 2009 sourcePartly supported

  The Introduction states that SNX-482-sensitive voltage-gated calcium channels are found in spine heads but not dendritic shafts. The Results and Discussion describe localized calcium influx involving voltage-sensitive sources and NMDARs, but the Discussion presents effects on plasticity-related signaling as a possibility, not a demonstrated outcome. The paper does not establish that these channels cooperate with other calcium channels to shape local depolarization and synaptic plasticity as claimed. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

Cdc42 activity remained spatially confined, because it had an intrinsic inactivation time constant of 6 s and therefore depends on continuous activation by CaMKII.

“Nevertheless, Cdc42 activity remained spatially confined, because it had an intrinsic inactivation time constant of 6 s and therefore depends on continuous activation by CaMKII (Murakoshi et al., 2011).”

• cites Murakoshi et al., 2011 sourcePartly supported

  The passage indexed under Abstract (page unavailable) says Cdc42 activity was confined to stimulated spines and infers an inactivation time constant of about 6 s. It concludes that Cdc42 must be continuously activated at those spines, but describes CaMKII signaling as transient; it does not say CaMKII continuously activates Cdc42. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

CaMKII is a calcium-activated kinase involved in structural plasticity by remodeling of the postsynaptic density, rearrangement of the actin cytoskeleton and maintenance of spine enlargement.

“CaMKII is a calcium-activated kinase involved in structural plasticity by remodeling of the postsynaptic density (Yoshimura et al., 2002), rearrangement of the actin cytoskeleton (Okamoto et al., 2007) and maintenance of spine enlargement (Matsuzaki et al., 2004; Lee et al., 2009).”

• cites Yoshimura et al., 2002 sourceNot checked — no full text of the source
• cites Okamoto et al., 2007 sourceSupported
• cites Matsuzaki et al., 2004 sourceNot checked — no full text of the source

May combine two claims.

CaMKII-Cdc42-Pak signaling increases spine volume and synaptic strength.

“CaMKII-Cdc42-Pak signaling increases spine volume and synaptic strength (Murakoshi et al., 2011)”

• cites Murakoshi et al., 2011 sourceSupported

May combine two claims.

The activation of Ras measured by FRET-FLIM was dependent on CaMKII activation, peaked later, and recovered to baseline level only after 15 min.

“The activation of Ras measured by FRET-FLIM was dependent on CaMKII activation, peaked later, and recovered to baseline level only after 15 min.”

• cites Harvey et al., 2008 sourcePartly supported

  The paper describes measuring Ras activation by FRET and fluorescence lifetime imaging (p. 1). It reports that a CaMKII inhibitor reduced Ras activation, which peaked within one minute of stimulation and returned to baseline within 15 minutes (p. 2). It does not establish that Ras peaked later than CaMKII, and “only after 15 min” overstates the reported return time. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Ras activity was shown to invade typically 10-20 neighboring spines in a range of 10 μm along the dendrite, whereas RhoA activity only spread 5 μm and rarely invaded neighboring spines.

“Ras activity was shown to invade typically 10–20 neighboring spines in a range of 10 μm along the dendrite, whereas RhoA activity only spread 5 μm and rarely invaded neighboring spines (Harvey et al., 2008; Murakoshi et al., 2011).”

• cites Harvey et al., 2008 sourcePartly supported

  The spatial-profile passage (p. 2) reports that Ras activity spread along the dendrite and invaded nearby spines, and the discussion (p. 4) describes a spread of about 10 μm. But the 10–20 synapses figure (p. 3) is an expectation for native Ras based on the authors’ analysis, not a directly observed typical count. The RhoA comparison is attributable to the other citation in the sentence, not to Harvey et al. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Murakoshi et al., 2011 sourcePartly supported

  The passages indexed under Abstract (page unavailable) report that HRas activity spreads into surrounding spines over about 10 μm, while RhoA activity spreads about 5 μm along the dendrite and invades adjacent spines only slightly. They do not support the specific claim that Ras activity typically invades 10–20 neighboring spines. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Ras diffusion rate out of the spine was relatively fast, reaching the dendrite within seconds without leaving any immobile fraction in the spine.

“Its diffusion rate out of the spine was relatively fast, reaching the dendrite within seconds without leaving any immobile fraction in the spine (Harvey et al., 2008).”

• cites Harvey et al., 2008 sourcePartly supported

  The mobility measurements (p. 2) show that Ras fluorescence decayed from the spine over seconds, and the discussion (p. 4) describes spine-to-dendrite diffusional coupling on a timescale of seconds. But the paper concludes only that there is no *major* immobile fraction: more than 90%, not all, of the measured fluorescence had left the spine after 30 seconds. It does not establish that there is no immobile fraction at all. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

The diffusion kinetics of both Cdc42 and Rho were comparable and similar to Ras diffusion and showed no immobile fraction left in the spine.

“Also the diffusion kinetics of both molecules were comparable and similar to Ras diffusion and showed no immobile fraction left in the spine.”

• cites Murakoshi et al., 2011 sourcePartly supported

  The diffusion-coupling passage reports that RhoA and Cdc42 were similarly mobile, with decay times comparable to a constitutively active HRas mutant. But it says 10–20% of fluorescence remained after 20 seconds, suggesting no *major* immobile fraction—not that no immobile fraction was left in the spine. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Downstream of CaMKII, Ras and Rho GTPases are important for regulating spine morphology and synaptic strength.

“Downstream of CaMKII, Ras and Rho GTPases are important for regulating spine morphology (Ramakers, 2002; Saneyoshi et al., 2010) and synaptic strength (Zhu et al., 2002; Patterson et al., 2010).”

• cites Ramakers, 2002 sourceNot checked — no full text of the source
• cites Saneyoshi et al., 2010 sourcePartly supported

  In “Regulation of spine and synapse formation by small GTPases” (page not provided), the review links CaMKII to Rac-regulating proteins involved in spine maturation and formation, and identifies Rho-family GTPases as regulators of spine morphology. It discusses Ras in relation to AMPA-receptor trafficking, but does not establish Ras as downstream of CaMKII in regulating spine morphology. The citing sentence attaches Saneyoshi et al. to spine morphology, not synaptic strength. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Zhu et al., 2002 sourceNot checked — no full text of the source

May combine two claims.

Long and thin necks prevent the diffusion of calcium, whereas shorter and thicker necks allow for better diffusional coupling with the dendrite.

“Nevertheless, morphology does play a role, as long and thin necks prevent the diffusion of calcium, whereas shorter and thicker necks allow for better diffusional coupling with the dendrite (Majewska et al., 2000; Holthoff et al., 2002; Sabatini et al., 2002; Korkotian et al., 2004; Noguchi et al., 2005).”

• cites Majewska et al., 2000 sourcePartly supported

  In “Functional regulation of calcium pumps and spine neck length” (page unavailable), the paper says diffusion between spine and dendrite depends on neck length, supporting the contrast between longer and shorter necks. It does not establish that long, thin necks prevent calcium diffusion or directly show that thicker necks improve coupling. The “Buffered calcium diffusion across the spine neck” section describes diffusion between the compartments, so “prevent” overstates the finding. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Holthoff et al., 2002 sourceNot checked — no full text of the source
• cites Sabatini et al., 2002 sourceNot checked — no full text of the source

May combine two claims.

A pool of synaptic receptors is immobile while another synaptic pool and extrasynaptic receptors are rapidly moving.

“A pool of synaptic receptors was shown to be immobile while another synaptic pool and extrasynaptic receptors were rapidly moving.”

• cites Tardin et al., 2003 sourceSupported

May combine two claims.

Voltage signals from the dendrite propagate without attenuation into spines, but synaptic potentials generated inside the spine head are filtered when they travel to the dendrite.

“This means that voltage signals from the dendrite propagate without attenuation into the spines (Holthoff et al., 2010; Carter et al., 2012; Popovic et al., 2014), but synaptic potentials generated inside the spine head are filtered when they travel to the dendrite (Araya et al., 2006, 2014; Harnett et al., 2012).”

• cites Holthoff et al., 2010 sourceNot checked — no full text of the source
• cites Carter et al., 2012 sourceCould not verify

  Carter et al. is cited for the first clause, about dendrite-to-spine voltage propagation; the second clause has separate citations. The Results section on single-spine glutamate uncaging reports EPSP amplification, but no passage found in our copy addresses whether dendritic voltage signals enter spines without attenuation (searched for dendrite-to-spine propagation and spine-neck attenuation). (LLM, conf=0.75)

  Experimental — accuracy not yet measured
• cites Popovic et al., 2014 sourceNot checked — no full text of the source

May combine two claims.

Takasaki and Sabatini find a weak decrease of recovery time with spine head volume, whereas the equation suggests a linear increase.

“However, whereas the equation suggests a linear increase of the recovery time scale with spine head volume, Takasaki and Sabatini (2014) instead find a weak decrease.”

• cites Takasaki and Sabatini, 2014 sourcePartly supported

  The Modeling of diffusive compartmentalization section gives equation (3), in which recovery time increases linearly with spine head volume when the other parameters are held fixed. In Results (Figure 2E), the measured association is weakly negative (r = −0.19), but it is not statistically significant (p = 0.26). Describing it as a decrease the authors ‘find’ overstates that result. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Glutamate stimulation enhances exchange between synaptic and extrasynaptic receptor pools and increases overall motility of glutamate receptors.

“Glutamate stimulation enhances the exchange between these pools and increases overall motility of glutamate receptors (Tardin et al., 2003).”

• cites Tardin et al., 2003 sourcePartly supported

  The Regulation of AMPARs mobility inside synapses section reports that bath-applied glutamate increased diffusion within synapses and reduced the proportion of immobile synaptic receptors. The Discussion links these changes to movement from synapses into extrasynaptic membrane, supporting enhanced exchange. But the same results section says extrasynaptic receptor diffusion was not significantly changed, so the claim of increased overall motility is broader than the finding. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Opening of sodium and calcium channels boosts local depolarization, while opening of potassium channels decreases local input resistance and results in smaller synaptic potentials.

“Opening of sodium and calcium channels boosts local depolarization (Araya et al., 2007; Bloodgood et al., 2009; Holbro et al., 2010; Carter et al., 2012; Hao and Oertner, 2012), while opening of potassium channels decreases local input resistance and results in smaller synaptic potentials (Ngo-Anh et al., 2005; Giessel and Sabatini, 2010).”

• cites Araya et al., 2007 sourceNot checked — no full text of the source
• cites Bloodgood et al., 2009 sourcePartly supported

  The Results section (‘Biphasic Synaptic Ca Influx and Graded Control by AMPARs’; page unavailable) says AMPARs modulate the amplitude of the synaptic potential in the spine, supporting a role for channel opening in local depolarization. But the paper describes voltage-gated calcium channels as being activated by synaptic depolarization, and says voltage-gated sodium channels were blocked in its experiments; it does not establish that opening both sodium and calcium channels boosts local depolarization. The potassium-channel clause is attributed to other citations, not this paper. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites Holbro et al., 2010 sourceNot checked — no full text of the source

May combine two claims.

There is an inverse relation between spine neck diameter d and recovery time, which appears to follow the predicted inverse quadratic relation (τ ∝ 1/d2).

“Indeed, both groups find an inverse relation between spine neck diameter d and the recovery time, which appears to follow the predicted inverse quadratic relation (τ ∝ 1/d2).”

• cites Takasaki and Sabatini, 2014 sourceSupported
• cites Tønnesen et al., 2014Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Truncated receptors void of any cytoplasmic tail can rescue the depletion of endogenous GluA1-3.

“a recent study suggests that truncated receptors void of any cytoplasmic tail can rescue the depletion of endogenous GluA1-3 (Granger et al., 2013).”

• cites Granger et al., 2013 sourceSupported

May combine two claims.

Receptor turnover in spines is slower compared to non-spinal plasma membrane, and recovery in the spine neck and base is particularly slow.

“Studying the FRAP dynamics of a fusion of SEP with the AMPA receptor subunit GluA2 (SEP-GluA2) revealed that receptor turnover in spines is slower compared to non-spinal plasma membrane and that recovery in the spine neck and base is particularly slow (Ashby et al., 2006).”

• cites Ashby et al., 2006 sourcePartly supported

  In “Lateral diffusion is compartmentalized at spines” and “Diffusion of AMPARs in and out of spines is limited by the neck” (pages unavailable), the paper reports slower AMPA-receptor exchange in spine heads than in nonspiny membrane and slower diffusion in the neck. It does not support particularly slow recovery at the neck base: the latter section reports that the base and dendritic shaft had indistinguishable fluorescence-loss rates, indicating relatively rapid equilibration outside the spine. The regional neck/base comparison used FLIP, not FRAP recovery. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

A fraction of spines strongly deviated from the average trends, suggesting that small local constrictions, local protein accumulations and organelle positioning in the neck may create additional diffusion barriers.

“Interestingly, a fraction of spines strongly deviated from the average trends that were observed (Takasaki and Sabatini, 2014), suggesting that small local constrictions, local protein accumulations and organelle positioning in the neck may create additional diffusion barriers (Arellano et al., 2007; Yuste, 2013).”

• cites Takasaki and Sabatini, 2014 sourceSupported
• cites Arellano et al., 2007 sourcePartly supported

  The Results (Analysis of spine neck lengths and diameters; page unavailable) say neck diameter varies along its length, supporting the possibility of local constrictions. The Introduction links spine necks to calcium compartmentalization, but our copy does not say that local protein accumulations or organelle positioning create additional diffusion barriers. The observation that some spines deviated from average trends is cited to Takasaki and Sabatini, not to Arellano. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites Yuste, 2013 sourceNot checked — no full text of the source

May combine two claims.

SEP fluorescence is quenched in acidified endosomal compartments but not in the extracellular environment after incorporation into the plasma membrane.

“whose fluorescence is quenched in the acidified endosomal compartments, but not in the extracellular environment after incorporation into the plasma membrane.”

• cites Miesenböck et al., 1998Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Ashby et al., 2004 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Crowding in the spine head may contribute to diffusional trapping of receptors.

“Based on results from modeling (Renner et al., 2009) it has been suggested that crowding in the spine head may contribute to this phenomenon (Colgan and Yasuda, 2014).”

• cites Renner et al., 2009 sourcePartly supported

  The Discussion says that obstacles at postsynaptic membranes increase apparent viscosity and favor receptor trapping. In “Diffusion of QD-ChTx depends on cytoskeleton integrity,” the authors describe the postsynaptic membrane as probably crowded and say crowding restricts diffusion. The copy does not establish crowding throughout the spine head or present this as a result of modeling; the reported measurements primarily track lipid-bound probes. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites Colgan and Yasuda, 2014 sourceSupported

May combine two claims.

Induction of plasticity results in an increase in spine size and changes in spine shape.

“Interestingly, induction of plasticity not only results in an increase in spine size (Matsuzaki et al., 2004; Tanaka et al., 2008), but also in changes in spine shape (Grunditz et al., 2008), with consequences for compartmentalization.”

• cites Matsuzaki et al., 2004 sourceNot checked — no full text of the source
• cites Tanaka et al., 2008 sourceSupported
• cites Grunditz et al., 2008 sourceSupported

May combine two claims.

The actin cytoskeleton mediates receptor positioning and its depolymerization reduces glutamate receptor accumulations in spines.

“Lastly, the actin cytoskeleton is known to mediate receptor positioning (Gudheti et al., 2013) and its depolymerization was shown to reduce glutamate receptor accumulations in spines (Allison et al., 2000).”

• cites Gudheti et al., 2013 sourcePartly supported

  The Introduction and the section on HA clusters show that actin affects the distribution and clustering of the membrane protein influenza hemagglutinin (HA). This supports the general idea of actin-mediated membrane-protein positioning, but the paper’s own findings concern HA, not receptor positioning specifically. The separate claim about glutamate receptors is attributed to Allison et al. (2000), not to this source. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites Allison et al., 2000 sourcePartly supported

  The introduction (page not specified) reports that AMPA-receptor clustering is strongly dependent on F-actin, citing the authors’ earlier study. But the Results section says NMDA-receptor NR2A clusters remained after actin depolymerization. The claim omits this receptor-type distinction and presents the reduction as a finding of the 2000 study itself. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Based on electron microscopy, three shape categories have been defined: thin, filopodia-like protrusions ("thin spines"), short spines without a well-defined spine neck ("stubby spines") and spines with a large bulbous head ("mushroom spines").

“Based on electron microscopy (EM), three shape categories have been defined: thin, filopodia-like protrusions (“thin spines”), short spines without a well-defined spine neck (“stubby spines”) and spines with a large bulbous head (“mushroom spines”) (Bourne and Harris, 2008).”

• cites Bourne and Harris, 2008 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Typical spine dimensions are ~<1 μm for the head diameter, and a ~100 nm wide and ~1 μm long spine neck, but notable differences in spine morphology exist.

“Typical dimensions are ~<1 μm for the head diameter, and a ~100 nm wide and ~1 μm long spine neck, but notable differences in spine morphology exist (Bourne and Harris, 2008).”

• cites Bourne and Harris, 2008 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S1 (asserted).

To what extent compartmentalization is governed by spine morphology, and in particular the diameter of the spine neck, has remained unresolved.

“However, to what extent compartmentalization is governed by spine morphology, and in particular the diameter of the spine neck, has remained unresolved.”

May combine two claims.

Because combining two-photon live imaging with post hoc serial sectioning EM requires fixing the sample, this approach might not detect all morphological changes that occur upon specific stimuli and is prone to morphological artifacts.

“As this requires fixing the sample, this approach might not detect all morphological changes that occur upon specific stimuli and is prone to morphological artifacts.”

May combine two claims.

RESOLFT requires orders of magnitude less light intensity and has been demonstrated on living brain slices.

“This approach requires orders of magnitude of less light intensity and has been demonstrated on living brain slices (Testa et al., 2012).”

• cites Testa et al., 2012 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

More recent modeling studies report that shape should also affect lateral diffusion of proteins embedded in the plasma membrane.

“In addition, more recent modeling studies report that shape should also affect lateral diffusion of proteins embedded in the plasma membrane (Kusters et al., 2013).”

• cites Kusters et al., 2013 sourceNot checked — no full text of the source

May combine two claims.

Not all neurons have spines (e.g., stellate neurons) and they can receive excitatory input directly on their shafts.

“However, not all neurons have spines (e.g., stellate neurons) and they can receive excitatory input directly on their shafts (Anderson et al., 1994).”

• cites Anderson et al., 1994 sourceNot checked — no full text of the source

May combine two claims.

More recent measurements have found neck diameters as low as 51 nm in organotypic cultures and 59 nm in acute slices.

“whereas more recent measurements have found neck diameters as low as 51 nm in organotypic cultures and 59 nm in acute slices (Tønnesen et al., 2014).”

• cites Tønnesen et al., 2014Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The actin cytoskeleton provides tracks for myosin-based transport of various cellular materials in and out of spines, including AMPA-type glutamate receptors.

“In addition, the actin cytoskeleton provides tracks for myosin-based transport of various cellular materials in and out of spines, including AMPA-type glutamate receptors (Kneussel and Wagner, 2013).”

• cites Kneussel and Wagner, 2013 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Rapid polymerization and depolymerization of actin filaments produces protrusive forces that can quickly change neuronal morphology.

“The rapid polymerization and depolymerization of actin filaments produces protrusive forces that can quickly change neuronal morphology (Kessels et al., 2011).”

• cites Kessels et al., 2011 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Neuronal activity in vitro and experience in vivo can alter spine morphology.

“For example, neuronal activity in vitro and experience in vivo can alter spine morphology (Holtmaat and Svoboda, 2009).”

• cites Holtmaat and Svoboda, 2009 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Two-color detection has been established using spectral unmixing of either pairs of organic dyes or the fluorescent proteins YFP and GFP.

“In addition, two-color detection has been established using spectral unmixing of either pairs of organic dyes (Tønnesen et al., 2011) or the fluorescent proteins YFP and GFP (Bethge et al., 2013).”

• cites Tønnesen et al., 2011Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Bethge et al., 2013 sourceNot checked — no full text of the source

May combine two claims.

A small neck should slow diffusion and result in functional compartmentalization by preventing signaling molecules to escape from the spine.

“A small neck should slow diffusion and result in functional compartmentalization by preventing signaling molecules to escape from the spine.”

May combine two claims.

Serial-sectioning EM directly visualizes all tissue surrounding spines as well as the structure of the postsynaptic specialization and has been used to identify precise morphological changes upon specific stimuli.

“Serial-sectioning EM directly visualizes all tissue surrounding spines as well as the structure of the postsynaptic specialization and has been used to identify precise morphological changes upon specific stimuli (Bourne and Harris, 2008).”

• cites Bourne and Harris, 2008 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Two-photon microscopy rapidly became the method of choice for deep tissue imaging and has even enabled intravital brain imaging in mice.

“Two-photon microscopy rapidly became the method of choice for deep tissue imaging and has even enabled intravital brain imaging in mice (Svoboda and Yasuda, 2006).”

• cites Svoboda and Yasuda, 2006 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The actin cytoskeleton plays a key role in shaping dendritic spines and is critically important for numerous processes that contribute to the plasticity of synaptic function.

“The actin cytoskeleton plays a key role in shaping dendritic spines and is critically important for numerous processes that contribute to the plasticity of synaptic function (Matus, 2000; Hering and Sheng, 2001; Luo, 2002; Ethell and Pasquale, 2005; Hotulainen and Hoogenraad, 2010).”

• cites Matus, 2000 sourceNot checked — no full text of the source
• cites Hering and Sheng, 2001 sourceNot checked — no full text of the source
• cites Luo, 2002 sourceNot checked — no full text of the source

May combine two claims.

Calcium can also be removed from spines by absorption into the smooth endoplasmic reticulum located in spines or by Na/Ca exchangers located in the plasma membrane.

“In addition to diffusion into the dendritic shaft, calcium can also be removed from spines by absorption into the smooth endoplasmic reticulum located in spines or by Na/Ca exchangers located in the plasma membrane (Sabatini et al., 2002).”

• cites Sabatini et al., 2002 sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

Lateral diffusion of receptors through the plasma membrane and activity-triggered exocytosis of receptors from internal endosomal compartments are generally accepted regulation mechanisms for synaptic plasticity.

“Lateral diffusion of receptors through the plasma membrane and activity-triggered exocytosis of receptors from internal endosomal compartments have become generally accepted regulation mechanisms for synaptic plasticity, although their respective contributions have remained unresolved”

• cites Passafaro et al., 2001 sourceNot checked — no full text of the source
• cites Borgdorff and Choquet, 2002 sourceNot checked — no full text of the source
• cites Adesnik et al., 2005 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The precise crosstalk and integration of Rho, Cdc42 and Rac is not completely understood.

“The precise crosstalk and integration is however not completely understood (Kennedy et al., 2005).”

• cites Kennedy et al., 2005 sourceNot checked — no full text of the source

May combine two claims.

The spread of signaling activity depends on three factors: (1) the extent and persistence of the upstream activation event; (2) the diffusion rate of the signaling molecule; and (3) its inactivation kinetics.

“The spread of their signaling activity depends on three factors: (1) the extent and persistence of the upstream activation event; (2) the diffusion rate of the signaling molecule; and (3) its inactivation kinetics, see Figure 1.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

If calcium-permeable ion channels were distributed equally throughout the plasma membrane, one would expect a higher effective concentration of these channels in spines compared to dendrites as the surface-to-volume ratio of the former is higher. This should theoretically lead to a higher influx of calcium in spines than in the surrounding dendrite.

“If these ion channels were distributed equally throughout the plasma membrane, one would expect a higher effective concentration of these channels in spines compared to dendrites as the surface-to-volume ratio of the former is higher. This should theoretically lead to a higher influx of calcium in spines than in the surrounding dendrite (Sabatini et al., 2002).”

• cites Sabatini et al., 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The high input resistance of spines may further facilitate synaptic potentials inside spines compared to equally strong synapses onto the dendritic shaft.

“In addition, the high input resistance of spines may further facilitate synaptic potentials inside spines compared to equally strong synapses onto the dendritic shaft.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Cytoplasmic tails of GluA receptors differentially regulate receptor diffusion and trapping at synapses.

“Whereas previously the cytoplasmic tails of GluA receptors have been shown to differentially regulate receptor diffusion and trapping at synapses (Passafaro et al., 2001)”

• cites Passafaro et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

Biochemical signaling, membrane-bound receptor dynamics and electrical signaling all contribute to proper information processing in the dendritic arbor and are interconnected.

“All of these levels contribute to proper information processing in the dendritic arbor and are interconnected.”

May combine two claims.

Tønnesen et al. report a quadratic dependence on head width w, whereas the model predicts a w3 dependence.

“Similarly, Tønnesen et al. (2014) report a quadratic dependence on head width w, whereas the model predicts a w3 dependence (assuming a spherical spine head in which V ∝ w3).”

• cites Tønnesen et al., 2014Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• AssumptionThe authors state this as an assumption: The spine head can be approximated as spherical for relating head width to volume.

May combine two claims.

Spine neck resistance values have varied over a wide range and are strongly influenced by the methods and theoretical models used.

“The resulting values for the spine neck resistance have varied over a wide range and are strongly influenced by the methods and theoretical models used.”

Classified as probably not a substantial claim.

Dendritic spines may serve as electrical compartments.

“In addition to inducing compartmentalization of biochemical signals and receptors, it has been suggested that dendritic spines may also serve as electrical compartments (Segev and Rall, 1998; Yuste, 2013).”

• cites Segev and Rall, 1998 sourceNot checked — no full text of the source
• cites Yuste, 2013 sourceNot checked — no full text of the source

May combine two claims.

Voltage-dependent ion channels are present within spines and activation of these channels results in a change of local membrane potential.

“Voltage-dependent ion channels are present within spines and activation of these channels results in a change of local membrane potential.”

May combine two claims.

AMPA receptors tagged with QDs selectively reduce their mobility at active synapses while freely diffusing through non-active synapses.

“AMPA receptors tagged with QDs were reported to selectively reduce their mobility at active synapse while they freely diffused through non-active synapses (Ehlers et al., 2007).”

• cites Ehlers et al., 2007 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing). May combine two claims.

The reduction in electrical compartmentalization occurs while chemical compartmentalization is preserved, reflecting two separate functions of spines within the dendrite.

“Interestingly, it was suggested that the reduction in electrical compartmentalization occurs while chemical compartmentalization is preserved, reflecting two separate functions of spines within the dendrite.”

May combine two claims.

Calcium elevations generally slow diffusion and locally accumulate AMPA receptors.

“Calcium elevations were shown to generally slow diffusion and locally accumulate AMPA receptors (Borgdorff and Choquet, 2002).”

• cites Borgdorff and Choquet, 2002 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

The respective contributions of lateral diffusion and activity-triggered exocytosis to synaptic plasticity remain unresolved.

“although their respective contributions have remained unresolved (Passafaro et al., 2001; Borgdorff and Choquet, 2002; Adesnik et al., 2005; Ashby et al., 2006; Park et al., 2006; Ehlers et al., 2007; Heine et al., 2008; Newpher and Ehlers, 2008; Yang et al., 2008; Kennedy et al., 2010; Opazo and Choquet, 2011; Czöndör et al., 2012; Czöndör and Thoumine, 2013).”

• cites Passafaro et al., 2001 sourceNot checked — no full text of the source
• cites Borgdorff and Choquet, 2002 sourceNot checked — no full text of the source
• cites Adesnik et al., 2005 sourceNot checked — no full text of the source

May combine two claims. The quote only partly states this claim.

Glutamate receptors reversibly stop at synaptic sites, modulated by neuronal activity levels that affect calcium transients.

“The earliest report used latex beads coupled to GluA2 receptors and found that these receptors reversibly stop at synaptic sites.”

May combine two claims.

Decreasing neck radius and increasing neck length effectively increase the confinement of receptors at the synapse.

“In combination with an exocytic event in the head of the spine, a decreasing neck radius and increasing neck length effectively increase the confinement of receptors at the synapse, as can be seen in Figure 3B showing the time-evolution of receptor concentration after the release of 1000 receptors at the top of the spine (Kusters et al., 2013).”

• cites Kusters et al., 2013 sourceNot checked — no full text of the source