The AMPA Receptor Code of Synaptic Plasticity

In the paper

“CNIH and TARPs likely compete for the same AMPAR binding sites (Straub and Tomita, 2012, Herring et al., 2013), and so one possible function of CNIH is to regulate the stoichiometry of TARP interaction, tuning the channel properties of the associated AMPARs.”

What the sources say

• Supported

  In “Roles of CNIH2/3 in regulating AMPA receptors in the brain” (page unavailable), the review says CNIH2 and TARPs interact competitively with AMPARs and that CNIH2/3 may displace TARPs to control TARP stoichiometry. The same section links TARP stoichiometry to channel properties, supporting the citing sentence’s hedged interpretation. (LLM, conf=0.88)

  cites Straub and Tomita, 2012 source
• Disputed

  The Results section (‘TARP γ-8 reverses…’; page unavailable) says that unchanged γ-8/AMPAR stoichiometry strongly argues CNIH-2 does not displace γ-8 and that the two can co-occupy GluA1 subunits. The Discussion (‘A model for the interaction…’; page unavailable) proposes four γ-8 molecules on the receptor combinations examined, contrary to CNIH regulating TARP stoichiometry by competing for those sites. The paper does report a different, subunit-specific interaction: γ-8 prevents CNIH from interacting with non-GluA1 subunits. (LLM, conf=0.89)

  Checked by a reasoning model — may be wrong.

  cites Herring et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“AMPARs are highly dynamic, undergoing continuous endocytosis, exocytosis, lateral diffusion in the plane of the membrane, reversible trapping at synapses at the post-synaptic density (PSD), and modifications in channel properties (Opazo et al., 2012, Huganir and Nicoll, 2013, Malinow and Malenka, 2002).”

What the sources say

• ?Not checked — no full text of the sourcecites Opazo et al., 2012 source
• Supported

  The Dynamic Regulation of AMPAR Membrane Trafficking section (page not supplied) describes rapid endocytosis, recycling to the membrane, lateral diffusion, and reduced mobility at synapses. Proposed Working Models for LTP says AMPARs enter and exit the PSD, while AMPAR Phosphorylation and LTP reports changes in channel conductance. (LLM, conf=0.91)

  cites Huganir and Nicoll, 2013 source
• ?Not checked — no full text of the sourcecites Malinow and Malenka, 2002 source

In the paper

“Interestingly, ubiquination and phosphorylation of GluA1 reciprocally inhibit each other indicating that a complex cross talk of GluA1 PTMs may regulate LTP expression (Guntupalli et al., 2017).”

What the sources say

• Partly supported

  The Results section, “The cross-talk between GluA1 phosphorylation and ubiquitination” (page unavailable), supports reciprocal inhibition at GluA1 Ser-845: ubiquitin-deficient mutants showed increased phosphorylation, while an S845D phosphomimetic showed reduced ubiquitination. The paper links this cross-talk to AMPA receptor trafficking and surface expression, but does not establish that it regulates LTP expression. (LLM, conf=0.85)

  cites Guntupalli et al., 2017 sourceExperimental — accuracy not yet measured

In the paper

“During hippocampal LTP, PKC is activated to increase GluA1 S818 phosphorylation and a peptide mimicking phospho-GluA1 S818 or shRNA-mediated knock-down of 4.1N both lead to decay of hippocampal LTP back to baseline, suggesting that the PKC/4.1N mediated increase in GluA1 exocytosis is necessary to maintain LTP (Lin et al., 2009, Boehm et al., 2006).”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Lin et al., 2009 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Boehm et al., 2006 source

In the paper

“AMPARs are substrates for cAMP-dependent kinase (PKA) and cGMP-dependent kinase (PKG) (GluA1 S845; GluA4 S842), protein kinase C (PKC) (GluA1 S818/S831/T840; GluA2 S863/S880), Ca++/calmodulin dependent kinase II (CaMKII) (GluA1 S567/S831), Casein kinase II (GluA1 S579; GluA2 S588), PAK3 (GluA1 S863), and Src family tyrosine kinase (GluA2 Y876) (Roche et al., 1996, Barria et al., 1997a, Barria et”

What the sources say

• Partly supported

  The Phosphorylation of Ser-845 and Ser-831 sections support PKA phosphorylation of GluR1 (GluA1) S845 and PKC phosphorylation of GluR1 S831. The cited paper also discusses CaMKII phosphorylation of GluR1 generally, but our copy does not establish the sentence’s other specified kinase–site pairings, including PKG, casein kinase II, PAK3, and Src pairings. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  cites Roche et al., 1996 sourceExperimental — accuracy not yet measured
• ?Not matched

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

  cites Barria et al., 1997a
• ?Not matched

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

  cites Barria et al., 1997b

In the paper

“These receptors have faster decay kinetics but large conductance, enhancing synaptic transmission, and may activate unique Ca2+-sensitive signaling pathways which lead to an opening of a metaplastic state, in which synapses become primed for LTD or LTP (Clem and Huganir, 2010, Sanderson et al., 2016).”

What the sources say

• ?Not matched

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

  cites Clem and Huganir, 2010
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Sanderson et al., 2016 sourceExperimental — accuracy not yet measured

In the paper

“GluA1 directly interacts with the cytoskeletal scaffold protein 4.1N through the C-terminal juxtamembrane region, and this interaction promotes activity-dependent exocytosis of GluA1 from intracellular endosomes (Lin et al., 2009, Anggono and Huganir, 2012).”

What the sources say

• Partly supported

  The Introduction and Results describe 4.1N binding to the membrane-proximal region of GluR1 (GluA1) and its role in activity-dependent insertion at the extrasynaptic surface. The Introduction says AMPARs are *thought* to originate from recycling endosomes, but the paper does not establish that the 4.1N-dependent GluR1 insertion events specifically come from intracellular endosomes. (LLM, conf=0.84)

  cites Lin et al., 2009 sourceExperimental — accuracy not yet measured
• Supported

  The Protein 4.1N section (page unavailable) says 4.1N binds directly to the membrane-proximal region of the GluA1 C-terminal domain and that its knockdown reduces GluA1 insertion into the plasma membrane. The AMPA Receptor Trafficking and AMPA Receptor Interacting Proteins sections (pages unavailable) describe delivery from AMPAR-containing vesicles or endosomes and GluA1’s role in activity-dependent exocytosis. (LLM, conf=0.86)

  cites Anggono and Huganir, 2012 source

In the paper

“These findings, together with several previous studies, support a model where PKA-mediated phosphorylation of GluA1 S845 promotes the surface trafficking of the receptor, lowering the threshold needed to induce LTP, however, additional signaling from CaMKII is needed to promote GluA1 targeting to the PSD for maximal LTP (Figure 1) (Sun et al., 2005, Oh et al., 2006, Esteban et al., 2003).”

What the sources say

• Partly supported

  The Discussion reports that D1–PKA signaling increases extrasynaptic GluR1 surface expression and that CaMKII is also needed for synaptic delivery. The section on D1 receptor stimulation shows that pretreatment enables a normally subthreshold glycine concentration to increase synaptic GluR1 incorporation. Our copy does not establish phosphorylation specifically at S845, directly measure a lowered LTP-induction threshold, or address maximal LTP or PSD targeting. (LLM, conf=0.88)

  cites Sun et al., 2005 sourceExperimental — accuracy not yet measured
• ?Not matched

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

  cites Oh et al., 2006
• ?Not checked — no full text of the sourcecites Esteban et al., 2003 source

In the paper

“NMDAR-dependent LTP requires Ca2+ influx leading to activation of CaMKII/PKC which directly phosphorylate GluA1 S831, increasing GluA1 single channel conductance and promoting GluA1 targeting to the PSD (Mammen et al., 1997, Barria et al., 1997a, Derkach et al., 1999, Kristensen et al., 2011, Barria et al., 1997b).”

What the sources say

• ?Not checked — no full text of the sourcecites Mammen et al., 1997 source
• ?Not matched

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

  cites Barria et al., 1997a
• Partly supported

  The Abstract and Results report that CaMKII phosphorylation of GluR1 (GluA1) at Ser-831 increases the contribution of higher single-channel conductance states. The paper also says PKC phosphorylates Ser-831, but treats its effect on conductance as presumptive. It does not establish NMDAR dependence or show that this phosphorylation promotes GluA1 targeting to the postsynaptic density. (LLM, conf=0.88)

  cites Derkach et al., 1999 sourceExperimental — accuracy not yet measured

In the paper

“The major form of LTP identified in the brain, NMDAR-dependent LTP, is the result of increased AMPAR density in the post-synaptic membrane and/or single channel conductance of the AMPAR (Huganir and Nicoll, 2013, Herring and Nicoll, 2016, Poncer et al., 2002, Benke et al., 1998).”

What the sources say

• Supported

  The Dynamic Regulation of AMPAR Membrane Trafficking section reports that AMPARs are recruited to synaptic spines after LTP induction, alongside synaptic strengthening. The AMPAR Phosphorylation and LTP section reports changes in AMPAR single-channel conductance after LTP and describes how phosphorylation regulates that conductance. Together, these passages support the stated postsynaptic mechanisms. (LLM, conf=0.86)

  cites Huganir and Nicoll, 2013 source
• ?Not checked — no full text of the sourcecites Herring and Nicoll, 2016 source
• Partly supported

  The introductory passage and Discussion describe increased synaptic AMPAR number and channel conductance as mechanisms associated with LTP in CA1 hippocampal neurons. The paper does not establish that these mechanisms explain NMDAR-dependent LTP throughout the brain; its own experiments test whether activated CaMKII mimics LTP-related effects in CA1 neurons. (LLM, conf=0.83)

  cites Poncer et al., 2002 sourceExperimental — accuracy not yet measured

In the paper

“TARPs have been shown to stabilize AMPARs both on the cell surface and at synapses (Bats et al., 2007, Sheng et al., 2018), and loss of TARPs results in decreased AMPAR expression, suggesting that “TARPless” AMPARs become unstable (Fukaya et al., 2006, Chen et al., 2000).”

What the sources say

• ?Not checked — no full text of the sourcecites Bats et al., 2007 source
• Partly supported

  The Discussion reports that the PDZ ligand of TARP γ-8 is essential for moving surface AMPARs to synapses, supporting the synaptic part of the claim. The Results report equal surface AMPAR currents with intact γ-8 and a PDZ-motif-deficient mutant; the paper does not establish that TARPs stabilize AMPARs on the cell surface. The decreased-expression and instability clause is attributed to other citations, not Sheng et al. (LLM, conf=0.86)

  cites Sheng et al., 2018 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section (‘Selective reduction of hippocampal AMPA receptors in γ-8-KO mice’; page unavailable) reports substantially lower hippocampal AMPA receptor levels after γ-8 deletion. The Discussion (‘Differences between the present and preceding studies’; page unavailable) suggests that receptors redistributed toward cell bodies are presumably degraded. The study does not establish that those receptors lack all TARPs or directly show that TARP-free receptors are unstable. (LLM, conf=0.84)

  cites Fukaya et al., 2006 sourceExperimental — accuracy not yet measured

In the paper

“TARPs and CNIH2/3 regulate AMPAR channel properties and cellular and synaptic trafficking (Straub and Tomita, 2012, Maher et al., 2017, Jacobi and von Engelhardt, 2017).”

What the sources say

• Partly supported

  The Conclusions state that TARPs modulate both AMPAR trafficking and channel properties, while CNIH2/3 modulate AMPAR channel properties. The section “Roles of CNIH2/3 in regulating AMPA receptors in the brain” reports enhanced AMPAR surface expression in heterologous cells but says whether CNIH2/3 promote trafficking in hippocampal neurons remains unresolved. Thus the claim overstates CNIH2/3’s established role in synaptic trafficking. (LLM, conf=0.86)

  cites Straub and Tomita, 2012 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Maher et al., 2017 source
• ?Not checked — no full text of the sourcecites Jacobi and von Engelhardt, 2017 source

In the paper

“This method would dramatically disrupt the composition of synapses and may not reflect the physiological mechanisms underlying LTP expression (Sheng et al., 2013).”

What the sources say

• Supported

  In “One step forward,” the paper says Granger et al. deleted the genes encoding three AMPA-receptor subunits, leaving endogenous AMPA receptors absent. In “Two steps back,” it cautions that this deletion may fundamentally change receptor trafficking compared with normal synapses and recommends subtler manipulations to study LTP mechanisms at normal synapses. Page numbers are not provided in our copy. (LLM, conf=0.91)

  cites Sheng et al., 2013 source

In the paper

“Phosphorylation of S845 increases single channel open–probability and also promotes GluA1 targeting or retention to the cell surface (Banke et al., 2000, Oh et al., 2006, Man et al., 2007).”

What the sources say

• Partly supported

  The Discussion states that phosphorylation of GluR1 Ser845 by PKA appears to increase peak open probability, supporting the first part of the sentence. The passages on recombinant receptor function and the additional search do not establish that Ser845 phosphorylation promotes targeting or retention at the cell surface. (LLM, conf=0.88)

  cites Banke et al., 2000 sourceExperimental — accuracy not yet measured
• ?Not matched

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

  cites Oh et al., 2006
• ?Not checked — no full text of the sourcecites Man et al., 2007 source

In the paper

“TARP γ-8 effectively prevented CNIH2/3 interaction with GluA2/3 heteromeric receptors suggesting that CNIH proteins may control the subunit composition of synaptic AMPARs (Herring et al., 2013).”

What the sources say

• Partly supported

  The Discussion’s model for GluA2A3 heteromers says the receptors did not coimmunoprecipitate CNIH-2 and proposes that they contain γ-8 but no CNIH, supporting the proposed link to synaptic AMPAR subunit composition. It calls γ-8’s inhibition of CNIH interaction with GluA3 speculative, however, so the claim presents that mechanism more definitively than the paper does. Page numbers were not available in our copy. (LLM, conf=0.82)

  cites Herring et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“The presence of perisynaptic CP-AMPARs as well as their recruitment to synapses requires signaling from PKA and the S845 phosphorylation site (He et al., 2009, Clem and Huganir, 2010, Sanderson et al., 2016).”

What the sources say

• ?Not matched

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

  cites He et al., 2009
• ?Not matched

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

  cites Clem and Huganir, 2010
• Partly supported

  The Introduction reports PKA-dependent recruitment of CP-AMPARs to synapses during LTD induction, and the Discussion says a perisynaptic CP-AMPAR pool was absent in S845A mice (page numbers unavailable). The paper does not establish that PKA signaling is required for the presence of that perisynaptic pool; it also acknowledges uncertainty about whether recruitment is physical or functional. (LLM, conf=0.83)

  cites Sanderson et al., 2016 sourceExperimental — accuracy not yet measured

In the paper

“S-nitrosylation of GluA1 C875 by nNOS was found to enhance the phosphorylation of GluA1 S831 by CaMKII (Figure 1) (Selvakumar et al., 2013), suggesting an additional synergistic relationship between S831 phosphorylation and C875 nitrosylation.”

What the sources say

• Partly supported

  The Results and Discussion report that nNOS-derived NO nitrosylates GluA1 at C875 and facilitates S831 phosphorylation. However, the direct phosphorylation experiments described in the Results used PKC stimulation; the CaMKII experiments measured changes in channel conductance, not a direct enhancement of CaMKII-mediated S831 phosphorylation by C875 nitrosylation. Page numbers were not available in our copy. (LLM, conf=0.85)

  cites Selvakumar et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“All four AMPAR subunit are also ubiquitinated. The major sites of ubiquitination on GluA1 and GluA2 have been mapped to GluA1 K868 and GluA2 K870/K882 (Widagdo et al., 2015, Widagdo et al., 2017, Lussier et al., 2015).”

What the sources say

• Supported

  The Results section, “All Four AMPAR Subunits Are Ubiquitinated in an Activity- and Ca2+-Dependent Manner,” reports ubiquitination of GluA1–4 after AMPA or bicuculline treatment. The Results section, “GluA1 and GluA2 Are Ubiquitinated on C-Terminal Lysine Residues,” identifies GluA1 Lys-868 and GluA2 Lys-870/Lys-882 as the major sites. (LLM, conf=0.95)

  cites Widagdo et al., 2015 source
• Supported

  The section “Ubiquitination of AMPARs Is Ca2+-Dependent” states that all four subunits, GluA1–4, undergo activity-dependent ubiquitination. It also identifies Lys-868 as the major GluA1 site and Lys-870 and Lys-882 as the predominant GluA2 sites in neurons. (LLM, conf=0.95)

  cites Widagdo et al., 2017 source
• Partly supported

  The Ubiquitination section (page not provided) reports that proteomic studies identified all four AMPAR subunits, GluA1–4, as ubiquitinated. Our copy does not identify GluA1 K868 or GluA2 K870/K882 as major ubiquitination sites; searches for those residues found no supporting passage. (LLM, conf=0.87)

  cites Lussier et al., 2015 sourceExperimental — accuracy not yet measured

In the paper

“Phosphorylation reduces the interaction with membrane lipids and facilitates interaction with PSD95, serving to trap the TARP/AMPAR complex with the PSD (Opazo et al., 2012, Bats et al., 2007, Sheng et al., 2018).”

What the sources say

• ?Not checked — no full text of the sourcecites Opazo et al., 2012 source
• ?Not checked — no full text of the sourcecites Bats et al., 2007 source
• Partly supported

  The Discussion (page not available) proposes that PSD-95 can capture AMPAR/TARP complexes through their PDZ ligands, supporting the trapping portion of the claim. It does not say that phosphorylation of the TARP C-terminus reduces membrane-lipid binding or facilitates PSD-95 binding; the phosphorylation described in that model is of synGAP. (LLM, conf=0.86)

  cites Sheng et al., 2018 sourceExperimental — accuracy not yet measured

In the paper

“Several major forms of LTD described in the brain including, cerebellar LTD and NMDAR-dependent and mGluR-dependent LTD, are expressed by a decrease in synaptic AMPAR content (Huganir and Nicoll, 2013).”

What the sources say

• Partly supported

  The NMDAR-Dependent LTD section says there is general consensus that LTD-related depression reflects a loss of synaptic AMPARs. The Cerebellar LTD section describes AMPAR endocytosis and retention of GluA2 inside the cell. Although it says mGluR1 activation induces cerebellar LTD, the passages do not establish the claim for mGluR-dependent LTD as a separately named form. (LLM, conf=0.83)

  cites Huganir and Nicoll, 2013 sourceExperimental — accuracy not yet measured

In the paper

“Recently, it has been found that LTP in cerebellar Purkinje neurons as well as cerebellar-dependent adaptation of the vestibulo-ocular reflex both depend on GluA3- but not GluA1-containing AMPARs (Gutierrez-Castellanos et al., 2017).”

What the sources say

• Supported

  The Introduction states that adaptation of compensatory eye movements depends on GluA3-containing, but not GluA1-containing, AMPARs, and that GluA3-containing AMPARs are critical for parallel-fiber–Purkinje-cell LTP. The Results section reports vestibulo-ocular learning deficits in GluA3-knockout mice but not GluA1-knockout mice. (LLM, conf=0.95)

  cites Gutierrez-Castellanos et al., 2017 source

In the paper

“Via its BAR-domain, PICK1 can either promote the invagination of the plasma membrane or direct GluA2 to regions of invagination where clathrin-mediated endocytosis occurs (Xia et al., 2000, Fiuza et al., 2017).”

What the sources say

• ?Not checked — no full text of the sourcecites Xia et al., 2000 source
• Partly supported

  The Introduction and Discussion (‘AMPAR clustering at CCPs’; page not provided) support PICK1-dependent targeting of GluA2-containing receptors to clathrin-coated endocytic sites, with AP2 binding at or adjacent to PICK1’s BAR domain. They do not establish that PICK1’s BAR domain itself promotes plasma-membrane invagination; the paper instead describes its interaction with dynamin and stimulation of dynamin polymerization. (LLM, conf=0.86)

  cites Fiuza et al., 2017 sourceExperimental — accuracy not yet measured

In the paper

“Here it was shown GluA3 containing receptors are mostly inert under basal conditions due to a very low-open probability, although these receptors are robustly targeted to synapses (Renner et al., 2017).”

What the sources say

• Supported

  The Results section reports that GluA2/3 receptors have a low open-channel probability under basal conditions and are largely electrically quiet. A separate Results section finds that they are constitutively inserted into synapses, supporting the claim that synaptic targeting occurs despite their low basal activity. (LLM, conf=0.94)

  cites Renner et al., 2017 source

In the paper

“Consistent with this model, genetic deletion of GRIP1/2 or PICK1 eliminates cerebellar LTD (Takamiya et al., 2008, Steinberg et al., 2006).”

What the sources say

• Supported

  The Results report that deleting both GRIP1 and GRIP2 abolished LTD in cultured mouse Purkinje cells; deleting either one alone did not. The Introduction also reports that mice lacking PICK1 do not express LTD, citing Steinberg et al. (2006) for that finding. (LLM, conf=0.92)

  cites Takamiya et al., 2008 source
• ?Not checked — no full text of the sourcecites Steinberg et al., 2006 source

In the paper

“This form of cerebellar LTP does not appear to involve trafficking of GluA3, but rather relies on an increase in the open-probability of GluA3-containing receptors through a cAMP-dependent pathway (Gutierrez-Castellanos et al., 2017).”

What the sources say

• Supported

  The Introduction states that PF–PC LTP depends on GluA3-containing receptors through changes in channel open probability rather than receptor trafficking, and requires cAMP-mediated Epac activation. The Discussion adds that the evidence against trafficking applies at least over tens of minutes, consistent with the citing sentence’s cautious wording. (LLM, conf=0.93)

  cites Gutierrez-Castellanos et al., 2017 source

In the paper

“Multiple studies have shown both in slice physiology experiments and in vivo that treatment with a short peptide mimicking the tyrosine-rich region of GluA2 (called the 3Y peptide) completely blocks LTD as well as activity-dependent GluA2 endocytosis (Fox et al., 2007, Ahmadian et al., 2004), while having no effect on basal synaptic transmission.”

What the sources say

• ?Not checked — no full text of the sourcecites Fox et al., 2007 source
• Partly supported

  The hippocampal-slice results (Figure 7) report that GluR2 3Y significantly reduced LFS-induced LTD, while the slice recordings (Figure 6) report no effect on basal synaptic transmission. The cultured-neuron experiments (Figure 8) show blockade of insulin-stimulated AMPA receptor endocytosis, not endocytosis directly measured after activity-induced LTD. This paper therefore does not establish complete blockade of activity-dependent endocytosis or provide in vivo evidence. (LLM, conf=0.88)

  cites Ahmadian et al., 2004 sourceExperimental — accuracy not yet measured

In the paper

“Data show that the amino terminal domain is not necessary for the formation of functional ion channels, or delivery onto the cell surface, but is required for targeting and retention of GluA1 at synapses during LTP (Watson et al., 2017, Diaz-Alonso et al., 2017).”

What the sources say

• Partly supported

  The Results section ('GluA1 requires the NTD for synaptic delivery'; page unavailable) shows that GluA1 lacking its N-terminal domain produces surface currents but fails to incorporate effectively at synapses. The LTP Results and Discussion show that potentiation cannot be maintained without the domain. However, the Discussion also reports transient potentiation and apparent synaptic incorporation of GluA1 lacking the domain, so the claim that it is required for initial targeting during LTP is too strong. (LLM, conf=0.85)

  cites Watson et al., 2017 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Diaz-Alonso et al., 2017 source

In the paper

“Interestingly, hippocampal mGluR-mediated LTD involves the dephosphorylation of GluA2 Y876 and is completely blocked by inhibitors of tyrosine phosphatases (Moult et al., 2006, Gladding et al., 2009).”

What the sources say

• Partly supported

  The section on DHPG-LTD and AMPAR dephosphorylation (page unavailable) reports reduced tyrosine phosphorylation of GluR2 in hippocampal slices, but does not identify residue Y876. The section on PTP inhibitors (page unavailable) reports that orthovanadate and phenylarsine oxide prevented significant DHPG-LTD, supporting the inhibitor-blockade portion under the tested conditions. (LLM, conf=0.88)

  cites Moult et al., 2006 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Gladding et al., 2009 source

In the paper

“Glutamate receptor agonists, including glutamate, AMPA and NMDA, induce GluA2 tyrosine phosphorylation which disrupts the interaction between GluA2 and GRIP1/2 but not PICK1 (Hayashi and Huganir, 2004).”

What the sources say

• Supported

  The ‘Activation of glutamate receptors’ section reports that glutamate, AMPA, and NMDA each increased GluR2 (GluA2) C-terminal tyrosine phosphorylation in cultured cortical neurons. The ‘Different regulation of GluR2-interacting molecules’ section reports that this phosphorylation impaired binding to GRIP1/2 but did not affect binding to PICK1. Page numbers were not available in our copy. (LLM, conf=0.93)

  cites Hayashi and Huganir, 2004 source

In the paper

“Phosphorylation of GluA2 S880 prevents GRIP1/2 binding and promotes the interaction of the GluA2 PDZ ligand with PICK1 (Seidenman et al., 2003, Chung et al., 2000, Steinberg et al., 2006), destabilizing GluA2 within the PSD and promoting GluA2 endocytosis.”

What the sources say

• Supported

  The Introduction states that S880 phosphorylation disrupts GluR2 binding to GRIP/ABP but not PICK1. The Discussion describes GRIP/ABP as anchoring GluR2 at synapses and proposes that phosphorylation shifts binding toward PICK1, increasing internalization and causing a net loss of synaptic receptors. Page numbers are not provided in the supplied passages. (LLM, conf=0.91)

  cites Seidenman et al., 2003 source
• Partly supported

  The binding-results section shows that Ser880 phosphorylation prevents GluR2 (GluA2) binding to GRIP1 while preserving binding to PICK1; it does not show increased PICK1 binding or test GRIP2. The Discussion and the section on PKC-induced internalization report increased GluR2 internalization alongside Ser880 phosphorylation, but do not establish that phosphorylation itself destabilizes GluR2 within the PSD or causes endocytosis. Page numbers were not available in our copy. (LLM, conf=0.89)

  cites Chung et al., 2000 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Steinberg et al., 2006 source

In the paper

“Mice lacking PICK1, KIBRA or Grasp1 all show reductions in hippocampal LTP as well as defects in hippocampus-dependent learning and memory tasks (Makuch et al., 2011, Volk et al., 2010, Chiu et al., 2017)”

What the sources say

• Supported

  Makuch et al. support the KIBRA portion of the multi-citation claim. The Results report reduced hippocampal LTP in adult KIBRA knockout mice and impaired retention in hippocampus-dependent fear-memory tasks; they note that the plasticity deficit was not seen in juvenile mice. The PICK1 and Grasp1 portions are attributed to the other citations, not judged here. (LLM, conf=0.94)

  cites Makuch et al., 2011 source
• Partly supported

  The Discussion reports impaired hippocampal LTP with a pairing protocol in adult PICK1-KO mice, while other LTP protocols showed no difference. The Results report impaired inhibitory-avoidance learning in adults, but neither LTP nor learning was impaired in juvenile PICK1-KO mice. The source therefore supports the PICK1 portion of the sentence, but not its unqualified implication that these deficits occur across ages or LTP protocols; the other genes are outside this source's attribution. (LLM, conf=0.87)

  cites Volk et al., 2010 sourceExperimental — accuracy not yet measured
• Supported

  Chiu et al. support the Grasp1 portion of the multi-citation sentence. In the Results sections on synaptic plasticity and cognitive function (pages not provided), Grasp1 knockout mice show reduced LTP and impaired performance on hippocampus-dependent learning and memory tasks. (LLM, conf=0.94)

  cites Chiu et al., 2017 source

In the paper

“GluA2 is also a target of ubiquitination on K870 and K882, which occurs in response to neuronal activity and is dependent on AMPAR internalization (Widagdo et al., 2015).”

What the sources say

• Supported

  The Results section identifies GluA2 K870 and K882 as major sites of AMPA-induced ubiquitination. A separate Results passage reports that blocking endocytosis abolished activity-induced AMPAR ubiquitination, demonstrating that it occurs after internalization. Page numbers are unavailable in our copy. (LLM, conf=0.94)

  cites Widagdo et al., 2015 source

In the paper

“Specifically, phosphorylation of GluA2 S880 is required as knock-in mutations that prevent phosphorylation of this site in mice (GluA2 K882A) eliminates cerebellar LTD (Chung et al., 2000, Steinberg et al., 2006).”

What the sources say

• Partly supported

  The ‘PKC phosphorylates serine-880 of GluR2’ section establishes phosphorylation at this site, and the Discussion suggests it may regulate AMPA-receptor internalization during synaptic plasticity. The paper does not establish that S880 phosphorylation is required for cerebellar LTD or report that a K882A knock-in eliminates it. (LLM, conf=0.89)

  cites Chung et al., 2000 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Steinberg et al., 2006 source

In the paper

“Scaling-up can be rescued by expression of shRNA-resistant WT GluA2, but not by a GluA2 chimera with the C-tail swapped for GluA1, suggesting that elements of the GluA2 C-terminus are required for scaling-up (Gainey et al., 2009).”

What the sources say

• Supported

  The Introduction states that shRNA-resistant GluR2 rescues scaling in GluR2-knockdown neurons, whereas a GluR2 chimera bearing the GluR1 C-terminal domain does not. The Results section, “The GluR2 C-Tail is required for the expression of synaptic scaling,” reports the same comparison and concludes that the GluR2 C-tail is essential. (LLM, conf=0.95)

  cites Gainey et al., 2009 source

In the paper

“A phosphorylation site was identified in the first intracellular loop of GluA1 (S567) which is phosphorylated by CaMKII and promotes removal of GluA1 from synapses (Lu et al., 2010, Coultrap et al., 2014).”

What the sources say

• ?Not matched

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

  cites Lu et al., 2010
• Supported

  The Results section reports CaMKII-dependent phosphorylation of GluA1 at S567 and identifies S567 as a CaMKII substrate site. The Discussion states that S567 phosphorylation decreases synaptic GluA1 localization and describes synaptic GluA1 removal by this phosphorylation. Page numbers are not provided in our copy. (LLM, conf=0.93)

  cites Coultrap et al., 2014 source

In the paper

“Scaling-up involves an increase in phosphorylation of GluA1 S845, but not S831, and is completely blocked in neurons with GluA1 S845A knock-in mutations, but remains intact in GluA1 S831A mutant neurons (Diering et al., 2014, Kim and Ziff, 2014).”

What the sources say

• Supported

  The Results section, “Changes in AMPAR phosphorylation during homeostatic scaling” (page unavailable), reports that 48 hours of TTX increased GluA1 S845 phosphorylation but not S831 phosphorylation. The Results section, “GluA1 phospho-S845 is required for scaling-up” (page unavailable), reports that TTX-induced scaling-up was eliminated in S845A knock-in neurons but remained normal in S831A neurons. (LLM, conf=0.94)

  cites Diering et al., 2014 source
• Partly supported

  The Results section, “pGluA1(S845) Is Required for TTX-Induced Synaptic Scaling” (page unavailable), reports increased S845 phosphorylation after TTX treatment and says TTX could not induce scaling in neurons from GluA1 S845A knock-in mice. Our copy does not address whether S831 phosphorylation increases or whether scaling remains intact in S831A mutant neurons (searched: S831 phosphorylation, S831A mutant neurons). (LLM, conf=0.88)

  cites Kim and Ziff, 2014 sourceExperimental — accuracy not yet measured

In the paper

“Bicuculline treatment stimulates GluA2 ubiquitination on K882 (Widagdo et al., 2015), very close to the Y876 and S880 phosphorylation sites, and AMPAR ubiquitination has been shown to be required for homeostatic scaling-down (Scudder et al., 2014).”

What the sources say

• Partly supported

  The Results section reports that bicuculline induces ubiquitination of GluA2, and a separate Results section identifies K882 as a major GluA2 ubiquitination site. However, the K882 mapping used AMPA treatment, not bicuculline, so the paper does not establish that bicuculline stimulates ubiquitination specifically at K882. The scaling-down statement is cited to Scudder et al., not to Widagdo et al. (LLM, conf=0.88)

  cites Widagdo et al., 2015 sourceExperimental — accuracy not yet measured
• Partly supported

  In the section on homeostatic downscaling (pages not supplied), the paper reports increased AMPAR ubiquitination after bicuculline treatment and shows that Nedd4-1 knockdown prevents downscaling of surface AMPARs and synaptic strength. It establishes that Nedd4-1 is required, but does not directly show that ubiquitination of AMPARs themselves is required. The GluA2 K882 claim is attributed to a different citation and is not part of this verdict. (LLM, conf=0.84)

  cites Scudder et al., 2014 sourceExperimental — accuracy not yet measured

In the paper

“GluA1 undergoes dephosphorylation of T840 and S845 during LTD by protein phosphatases PP1/PP2A and CaN, respectively (Delgado et al., 2007, Toda and Huganir, 2015, Lee et al., 1998, Sanderson et al., 2016).”

What the sources say

• Partly supported

  The Results sections on chem-LTD and T840 phosphatases report persistent T840 dephosphorylation during chemical LTD and show that inhibiting PP1/PP2A prevents NMDA-induced T840 dephosphorylation. They do not establish the same change during synaptically induced LTD, and the paper does not identify CaN as the phosphatase responsible for S845 dephosphorylation. (LLM, conf=0.87)

  cites Delgado et al., 2007 sourceExperimental — accuracy not yet measured
• Partly supported

  The Abstract links S845 phosphorylation changes to LTD, and the Results report that a PP1/PP2A inhibitor blocks T840 dephosphorylation after PACAP38 stimulation. The paper does not establish that PP1/PP2A dephosphorylates T840 during LTD or that CaN dephosphorylates S845 during LTD; the Discussion describes PACAP38’s possible role in LTD as conceivable and requiring further study (page numbers unavailable). (LLM, conf=0.88)

  cites Toda and Huganir, 2015 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Lee et al., 1998 source

In the paper

“Neither GRIP1/2 nor PICK1 are required for scaling-down (Tan et al., 2015, Anggono et al., 2011).”

What the sources say

• Supported

  The Discussion says that downscaling remains intact in GRIP knockout neurons and describes PICK1 as dispensable for scaling down. The results section also reports intact bicuculline-induced scaling down regardless of GRIP expression. (LLM, conf=0.93)

  cites Tan et al., 2015 source
• Partly supported

  The Results report robust scaling-down after bicuculline treatment in PICK1 knockout neurons, supporting the PICK1 part of the sentence. The cited paper does not establish that GRIP1/2 are dispensable for scaling-down, so it does not support the full claim attributed jointly to the two citations. (LLM, conf=0.84)

  cites Anggono et al., 2011 sourceExperimental — accuracy not yet measured

In the paper

“Scaling-up appears to involve increased tyrosine phosphorylation of GluA2 as a result of downregulation of the tyrosine phosphatase, STEP61 (Figure 3), and scaling-up could be blocked by exogenously applied STEP61 (Jang et al., 2015).”

What the sources say

• Partly supported

  The Results and discussion report that activity blockade reduced STEP61 and increased GluA2 tyrosine phosphorylation, and that TAT-STEP WT preincubation abolished TTX-induced synaptic scaling. However, the applied TAT-STEP protein was a STEP46 fusion, not exogenously applied STEP61 as the claim specifies. Page numbers were not provided in our copy. (LLM, conf=0.86)

  cites Jang et al., 2015 sourceExperimental — accuracy not yet measured

In the paper

“Despite the fact that both GluA1 and GluA2 have been implicated in homeostatic scaling-up, complete knock-out of GluA1 still allowed for the scaling-up of GluA2/3, and complete knock-out of GluA2/3 still allowed for the scaling-up of GluA1 (Altimimi and Stellwagen, 2013), suggesting that regulatory elements in GluA1/2 can be circumvented by complete removal of these subunits.”

What the sources say

• Supported

  The Results report increased GluA2 surface expression in GluA1-knockout cultures and increased GluA1 surface expression in GluA2/GluA3 double-knockout cultures after activity blockade. The Discussion states that synaptic scaling was preserved despite these constitutive deletions (article pp. 11763–11767). (LLM, conf=0.94)

  cites Altimimi and Stellwagen, 2013 source

In the paper

“Concomitantly, GRIP1 protein is upregulated during scaling-down, but remains in intracellular compartments where it may act to sequester internalized GluA2-containing receptors away from the synapse (Figure 3) (Tan et al., 2015).”

What the sources say

• Partly supported

  The section on GRIP1 subcellular distribution (Fig. 4) reports that scaling down increases cytoplasmic GRIP1 and decreases synaptic GRIP1. It describes a cytoplasmic GRIP1 pool that can retain AMPARs intracellularly, but does not show that the increased pool sequesters internalized GluA2-containing receptors during scaling down; it instead reports reduced overall GRIP1–GluA2 interaction. (LLM, conf=0.84)

  cites Tan et al., 2015 sourceExperimental — accuracy not yet measured

In the paper

“Scaling-up can be blocked by the expression of the soluble cytosolic C-terminal tail of GluA2 or by shRNA-mediated knock-down of GluA2 (Gainey et al., 2009, Ancona Esselmann et al., 2017).”

What the sources say

• Supported

  The Results section (‘The GluR2 C-tail but not the GluR1 C-tail blocks synaptic scaling’; page not provided) reports that expression of a GluR2 C-tail peptide completely blocked scaling. The Results section on GluR2 knockdown likewise reports that shRNA-mediated knockdown prevented the TTX-induced increase in mEPSC amplitude. (LLM, conf=0.94)

  cites Gainey et al., 2009 source
• ?Not checked — no full text of the sourcecites Ancona Esselmann et al., 2017 source

In the paper

“GluA1 T840 phosphorylation has been shown to increase GluA1 single channel conductance while phosphorylation of S845 increases channel open probability, suggesting that dephosphorylation of these sites might also be important to reduce ion channel properties for expression of LTD (Banke et al., 2000, Jenkins et al., 2014).”

What the sources say

• Partly supported

  The Discussion states that phosphorylation of GluR1 Ser845 increases peak open probability, supporting the S845 part of the claim. The paper does not address T840 phosphorylation or attribute increased single-channel conductance to T840; its Discussion instead associates increased unitary conductance with Ser831 phosphorylation. (LLM, conf=0.87)

  cites Banke et al., 2000 sourceExperimental — accuracy not yet measured
• Supported

  The Results report increased conductance with a Thr840 phosphomimetic mutation and increased open probability with a Ser845 phosphomimetic mutation. The Discussion interprets these findings as Thr840 phosphorylation increasing conductance and Ser845 phosphorylation enhancing open probability. The experiments used phosphomimetic substitutions rather than directly measuring both effects after phosphorylation. (LLM, conf=0.91)

  cites Jenkins et al., 2014 source

In the paper

“During the induction phase of LTD, transient signaling from synaptic CP-AMPARs is required for the full expression of LTD, and during the progression of LTD induction these CP-AMPARs signal their own removal through activation of calcineurin (CaN) (Sanderson et al., 2016).”

What the sources say

• Supported

  The Discussion states that CP-AMPAR signaling during LTD induction is required for robust LTD expression and helps trigger AKAP-anchored calcineurin-mediated removal of the newly recruited receptors. The Results likewise describe calcium signaling by recruited CP-AMPARs as helping determine LTD expression before triggering their own removal. (LLM, conf=0.94)

  cites Sanderson et al., 2016 source

In the paper

“CaMKII is well known to be required for LTP, but its activity is also required during LTD where a prolonged “weak” stimulus favors the phosphorylation of GluA1 S567 over S831, leading to removal of synaptic GluA1 (Coultrap et al., 2014).”

What the sources say

• Supported

  The Results section, “CaMKII is required for LTD,” reports that CaMKII inhibition blocked NMDAR-dependent LTD in hippocampal CA1. The Results section on differential biochemical regulation says weak, prolonged LTD-type stimuli favor GluA1 S567 over S831 phosphorylation; the Discussion says S567 phosphorylation decreases synaptic AMPAR localization. The demonstrated requirement is specifically for the NMDAR-dependent form of LTD studied here. (LLM, conf=0.91)

  cites Coultrap et al., 2014 source

In the paper

“Prolonged TTX treatment in cultured neurons causes lysosomal degradation of PICK1, while deletion of PICK1 enhances mEPSC amplitude and occludes homeostatic scaling-up, suggesting that decreased activity of PICK1 is an important mediator of scaling-up (Figure 3) (Anggono et al., 2011).”

What the sources say

• Supported

  In Results, “Neuronal activity regulates PICK1 protein level in cultured neurons” (Fig. 1E,F), prolonged TTX treatment reduced PICK1, and a lysosomal inhibitor largely prevented that reduction. In Results, “TTX-induced synaptic scaling is occluded in PICK1 knockout neurons” (Fig. 2A–C), knockout neurons had higher basal mEPSC amplitudes and did not show the TTX-induced scaling-up seen in wild-type neurons. The Discussion proposes that reduced PICK1 during inactivity helps promote receptor accumulation, consistent with the citing sentence’s interpretation. (LLM, conf=0.92)

  cites Anggono et al., 2011 source

In the paper

“Homeostatic scaling-up has also been observed in the visual cortex in mice in response to visual deprivation, and involves the recruitment of synaptic CP-AMPARs and increased GluA1 S845 phosphorylation (Goel et al., 2006, Goel et al., 2011).”

What the sources say

• ?Not checked — no full text of the sourcecites Goel et al., 2006 source
• Supported

  The Discussion reports that visual deprivation-induced scaling up in the mouse visual cortex was associated with increased GluR1 (GluA1) S845 phosphorylation and accompanied by synaptic incorporation of Ca2+-permeable GluR1-homomers. This supports both mechanisms attributed to the paper. (LLM, conf=0.94)

  cites Goel et al., 2011 source

In the paper

“TTX-induced homeostatic scaling-up in cultured neurons increases GluA1 protein expression as well as surface and synaptic levels of CP-AMPARs (GluA1 homomers) and GluA1/2 heteromers but not in GluA3-containing AMPARs (Figure 3) (Diering et al., 2014, Soares et al., 2013, Tan et al., 2015, Kim and Ziff, 2014, Hu et al., 2010).”

What the sources say

• Partly supported

  The Results section, “Changes in AMPAR phosphorylation during homeostatic scaling” (page unavailable), reports that 48 hours of TTX increased surface GluA1 and GluA2 but not GluA3, consistent with GluA1/2-containing receptors rather than GluA2/3-containing receptors. Other Results passages report synaptic recruitment of GluA1 and changes in total AMPAR expression, but do not establish increased total GluA1 specifically or increased surface and synaptic levels of both GluA1 homomers (CP-AMPARs) and GluA1/2 heteromers. (LLM, conf=0.85)

  cites Diering et al., 2014 sourceExperimental — accuracy not yet measured
• Partly supported

  In “Homeostatic upregulation of synaptic GluA2-lacking AMPARs” (page unavailable), the paper reports increased total and surface GluA1 after TTX treatment and evidence of synaptic GluA2-lacking AMPARs in organotypic hippocampal slices. It does not establish that these receptors are specifically GluA1 homomers, that GluA1/2 heteromers increase, or that GluA3-containing AMPARs do not increase. The claim also describes cultured neurons more broadly than the slice preparation studied. (LLM, conf=0.88)

  cites Soares et al., 2013 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section reports that chronic TTX increased total GluA1 and surface GluA1 and GluA2, but not surface GluA3. The Discussion interprets the surface changes as preferential GluA1/GluA2 heteromer insertion. It does not establish increased surface or synaptic GluA1-homomer CP-AMPARs; instead, it says their synaptic insertion was unlikely to predominate (page numbers unavailable). (LLM, conf=0.88)

  cites Tan et al., 2015 sourceExperimental — accuracy not yet measured

In the paper

“Dephosphorylation of GluA2 S880 during scaling-down is mediated by activation of phosphatase PP1, through its regulatory protein inhibitor 2 (I-2) (Siddoway et al., 2013), while dephosphorylation of GluA2 Y876 requires an upregulation of STEP61 (Jang et al., 2015).”

What the sources say

• Supported

  The Results (Fig. 3J,K) state that I-2 phosphorylation activates PP1, which dephosphorylates GluA2 at S880; blocking I-2 phosphorylation attenuated that dephosphorylation. The paper also links this pathway to synaptic downscaling. The STEP61 clause is attributed to Jang et al., not to this source. (LLM, conf=0.94)

  cites Siddoway et al., 2013 source
• Partly supported

  The Jang citation attaches to the STEP61/GluA2 Y876 clause, not the PP1/I-2 clause. In Results and discussion (page not supplied), increased STEP61 coincided with reduced phosphorylation of GluA2 at a three-tyrosine site that includes Y876. The authors say the specific GluA2 tyrosine residues regulated by STEP61 are unknown, and inhibiting STEP did not block the measured reduction in three-tyrosine phosphorylation; the paper therefore does not establish that Y876 dephosphorylation requires STEP61 upregulation. (LLM, conf=0.88)

  cites Jang et al., 2015 sourceExperimental — accuracy not yet measured

In the paper

“Bicuculline-induced scaling-down in cultured neurons involves the downregulation of GluA1/2/3 protein levels as well a reduced synaptic targeting of all AMPAR subunits (Diering et al., 2014, Tan et al., 2015).”

What the sources say

• Partly supported

  The Results section, “Changes in AMPAR phosphorylation during homeostatic scaling” (page unavailable), reports that bicuculline reduced cell-surface GluA1, GluA2 and GluA3 in cultured neurons. “GluA1 phospho-S845 is required for scaling-up” mentions changes in total AMPAR expression but does not specify downregulation of all three subunits. The copy documents reduced PSD-associated GluA1, not reduced synaptic targeting of every subunit. (LLM, conf=0.85)

  cites Diering et al., 2014 sourceExperimental — accuracy not yet measured
• Partly supported

  The ‘Inactivity-Induced Synaptic Scaling Is Blocked in GRIP Knockout’ section reports that bicuculline reduced total GluA1, GluA2, and GluA3 expression and reduced surface levels of all three in cultured neurons (Fig. S1; Fig. 3 A–D). It does not establish reduced synaptic targeting of each subunit specifically; the reported subunit-specific measurements are of surface levels. (LLM, conf=0.84)

  cites Tan et al., 2015 sourceExperimental — accuracy not yet measured

In the paper

“AMPARs play an essential role in the functioning of the brain, and changes in the abundance of post-synaptic AMPARs are a fundamental mechanism for most forms of synaptic plasticity (Huganir and Nicoll, 2013).”

What the sources say

• Partly supported

  The Conclusions and Future Directions section says changes in AMPAR number at synaptic spines mediate changes in strength during LTP and LTD. The Proposed Working Models for LTP section calls AMPAR regulation key to many forms of synaptic plasticity and important for learning and memory, but it does not establish the claim’s stronger scope of “most forms.” Page numbers are unavailable in our copy. (LLM, conf=0.84)

  cites Huganir and Nicoll, 2013 sourceExperimental — accuracy not yet measured

In the paper

“Thus the “slot hypothesis” offers some explanation for the prominent role of GluA1 in LTP and of GluA2 in LTD, via the rapid activity-dependent mobilization of GluA1-containing receptors onto the cell surface during LTP, and the removal of GluA2 containing receptors from the cell-surface during LTD through interactions with AP2 and/or through interactions involving the GluA2 Y-rich motif (Ahmadian”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Ahmadian et al., 2004 source
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Anggono and Huganir, 2012 sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Huganir and Nicoll, 2013 sourceExperimental — accuracy not yet measured

In the paper

“Synaptic GluA1 is dephosphorylated at S831 and S845 during scaling-down and also in the forebrain during sleep (Diering et al., 2014, Diering et al., 2017), which together with other observations suggests that homeostatic scaling-down occurs across the forebrain during sleep (Diering et al., 2017).”

What the sources say

• Partly supported

  The Results section, “Changes in AMPAR phosphorylation during homeostatic scaling” (page unavailable), reports decreased GluA1 phosphorylation at both S831 and S845 after bicuculline-induced scaling-down. It does not establish that both decreases occurred specifically in synaptic GluA1. The sleep finding is separately attributed to Diering et al. (2017), not to this source. (LLM, conf=0.82)

  cites Diering et al., 2014 sourceExperimental — accuracy not yet measured
• Supported

  The passage labeled Abstract describes AMPAR dephosphorylation during homeostatic scaling-down and reports decreased synaptic GluA1 phosphorylation at S845 and S831 in mouse forebrain PSD samples collected during sleep versus wake. It also says the forebrain changes were examined because they had previously been observed during scaling-down in vitro. (LLM, conf=0.91)

  cites Diering et al., 2017 source

In the paper

“Forms of LTP, LTD and homeostatic scaling have been shown to be intact in knock-out mice of different AMPAR subunits as well as in using molecular replacement experiments (Huganir and Nicoll, 2013, Granger et al., 2013, Ancona Esselmann et al., 2017).”

What the sources say

• Partly supported

  In “Subunit Dependence of AMPAR Trafficking and LTP and LTD” (page unavailable), the review reports that molecular replacement found no specific AMPAR-subunit requirement for LTP. “NMDAR-Dependent LTD” reports normal LTD in mice lacking GluA2/GluA3 or GluA1. The review describes homeostatic synaptic scaling in “Dynamic Regulation of AMPAR Membrane Trafficking,” but does not say it remains intact in AMPAR-subunit knockout mice or molecular replacement experiments. (LLM, conf=0.88)

  cites Huganir and Nicoll, 2013 sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction and the section “LTP requires a reserve pool of AMPARs” report normal LTP with some molecular replacements and with GluA2 or GluA3 deletion. But the latter section reports impaired LTP after GluA1 deletion, so the knockout claim is too broad. The paper does not establish intact LTD or homeostatic scaling in these experiments. (LLM, conf=0.91)

  cites Granger et al., 2013 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Ancona Esselmann et al., 2017 source

In the paper

“GluA2-containing receptors (likely GluA2/3 heteromers) undergo spontaneous and constitutive exocytosis, but these events are much smaller, containing an estimated 2-5 receptors (Araki et al., 2010, Gu et al., 2016, Lin et al., 2009).”

What the sources say

• Partly supported

  The Discussion reports that GluA2 exocytosis is largely constitutive (approximately 70%) and that its insertion events contain only a few receptors compared with GluA1; it also discusses GluA2/3 heteromers. The Results report lower fluorescence intensity for GluA2 events, but our copy does not give the claimed estimate of 2–5 receptors per event. (LLM, conf=0.87)

  cites Araki et al., 2010 sourceExperimental — accuracy not yet measured
• ?Not matched

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

  cites Gu et al., 2016
• Partly supported

  In Results, under “Capturing insertion events of GluRs” (page unavailable), the paper associates GluR2 with constitutive trafficking but says it rarely observed GluR2 insertion under normal conditions. It does not identify those receptors as likely GluR2/3 heteromers or support the estimate of 2–5 receptors per event. (LLM, conf=0.86)

  cites Lin et al., 2009 sourceExperimental — accuracy not yet measured

In the paper

“Interestingly, GluA1 which remains phosphorylated is resistant to scaling-down and the unphosphorylated GluA1 containing receptors are preferentially removed (Figure 4) (Diering et al., 2014).”

What the sources say

• Supported

  The Results section, “Phospho-S845 GluA1 is resistant to scaling-down,” reports that phosphorylated receptors remained on the cell surface while overall surface GluA1 decreased. The Discussion, “AMPAR phosphorylation and global synaptic plasticity,” explicitly concludes that non-phosphorylated receptors are preferentially removed and PKA-phosphorylated receptors resist scaling-down. The finding is described under conditions of high PKA activity; page numbers are not provided in our copy. (LLM, conf=0.94)

  cites Diering et al., 2014 source

In the paper

“GluA2 can directly interact with AP-2 clathrin adapter complex, which allows GluA2-containing receptors to be rapidly depleted from the cell-surface (Kastning et al., 2007, Lee et al., 2002).”

What the sources say

• Supported

  The Results show that the GluR2 cytoplasmic tail binds directly to the μ2 subunit of AP-2. The Discussion describes rapid AP-2-dependent AMPA receptor recycling and reports that disrupting AP-2 binding increases surface GluR levels, supporting the claimed role in removal from the cell surface. (LLM, conf=0.87)

  cites Kastning et al., 2007 source
• ?Not checked — no full text of the sourcecites Lee et al., 2002 source

In the paper

“Four subunits, GluA1-4, assemble into tetramers to make up the core functional ion channel, with different combinations conferring unique cellular trafficking behaviors and biophysical characteristics (Shepherd and Huganir, 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites Shepherd and Huganir, 2007 source

In the paper

“Layers of regulation are added to AMPAR tetramers through these different interactions and modifications, increasing the computational power of synapses.”

In the paper

“In some cases, it has been shown that certain AMPAR PTMs can influence others (Figure 1C), either by inhibiting or promoting the neighboring modification, suggesting that of all possible AMPARs variants some will be favored.”

In the paper

“AMPAR subunits contain highly conserved ligand binding and transmembrane domains that allow glutamate binding and channel pore assembly respectively, but are divergent in their extracellular amino-terminal domains and cytoplasmic carboxy-terminal tails which are subject to PTMs (Shepherd and Huganir, 2007) (Figure 1).”

What the sources say

• ?Not checked — no full text of the sourcecites Shepherd and Huganir, 2007 source

In the paper

“Earlier studies suggest that long-tailed AMPARs are recruited to synapses in an activity-dependent manner, while short-tailed AMPARs undergo constitutive cycling in and out of synapses (Shi et al., 2001, Hayashi et al., 2000).”

What the sources say

• ?Not checked — no full text of the sourcecites Shi et al., 2001 source
• ?Not checked — no full text of the sourcecites Hayashi et al., 2000 source

In the paper

“The dynamic nature of AMPARs suggests that the AMPAR code will function by shifting equilibriums in favor of synaptic accumulation or removal, and by altering ion channel properties.”

In the paper

“recent data from Zhou et al., provide strong evidence that the GluA1 C-terminal tail is both necessary and sufficient for hippocampal LTP (Zhou et al., 2017).”

What the sources say

• ?Not matched

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

  cites Zhou et al., 2017

In the paper

“The result of this modification is that GluA2 containing receptors have a linear current-voltage (I-V) relationship and are impermeable to Ca2+, while GluA2-lacking receptors show high conductance and rapid decay kinetics, inward-rectification due to voltage-dependent block by intracellular polyamines and are permeable to Ca2+, thus GluA2-lacking receptors are usually referred to as calcium-perme”

What the sources say

• ?Not checked — no full text of the sourcecites Burnashev et al., 1992 source

In the paper

“For each type of plasticity, certain AMPAR variants will be preferentially added or removed from synapses or undergo selective changes in channel properties.”

In the paper

“Incredibly, LTP was rescued in GluA1C2KI and GluA2C1KI double mutant mice, showing that the C-tail of GluA1 is sufficient for LTP expression, even when it is attached to the GluA2 subunit (Zhou et al., 2017).”

What the sources say

• ?Not matched

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

  cites Zhou et al., 2017

In the paper

“As an example, GluA1 undergoes 11 known PTMs each of which can occur independently and reversibly (7 phosphorylations, 2 palmitoylations, 1 S-nitrosylation, 1 ubiquitination), allowing for 211, or 2,048 possible modified variants of GluA1”

In the paper

“Thus, while phosphorylation of GluA1 S831 or S845 are clearly involved in LTP, the strict requirement for each site as well as the synergistic effects of dual phosphorylation are likely synapse- and induction-specific.”

In the paper

“Importantly, LTP was completely absent in GluA1C2KI mice, demonstrating that the GluA1 C-tail is necessary for LTP.”

What the sources say

• ?Not matched

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

  cites Zhou et al., 2017

In the paper

“All four AMPAR subunits are palmitoylated at a conserved cysteine residue in the C-terminal juxtamembrane region (GluA1 C811, GluA2 C836, GluA3 C841, GluA4 C817) and a second site within the transmembrane domain TM2 (Hayashi et al., 2005).”

What the sources say

• ?Not checked — no full text of the sourcecites Hayashi et al., 2005 source

In the paper

“Therefore, synaptic potentiation through GluA3 may not require AMPAR trafficking, but rather cAMP-dependent enhancement of channel open-probability of GluA3-containing receptors already localized to synapses, allowing for very rapid changes in synaptic efficacy.”

In the paper

“This mechanism likely also applies to GluA3, which also interacts with GRIP1/2 and PICK and the phosphorylation site, S885 is conserved with GluA2 S880 (Figure 1B).”

In the paper

“AMPARs must be removed from the PSD, allowing for lateral diffusion away from the synapse, and concomitantly, AMPARs are locally depleted from the cell-surface by clathrin- and dynamin-dependent endocytosis (Shepherd and Huganir, 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites Shepherd and Huganir, 2007 source

In the paper

“If PKA is not able to phosphorylate GluA1 S845, CP-AMPAR recruitment to synapses during LTD is blocked, possibly explaining the complete absence of LTD in GluA1 S845A knock-in mice.”

In the paper

“Hippocampal LTD is still observed in knock-outs of GluA2/3 (Meng et al., 2003), but not in neurons expressing GluA2 fused to the GluA1 C-tail (Zhou et al., 2017).”

What the sources say

• ?Not checked — no full text of the sourcecites Meng et al., 2003 source
• ?Not matched

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

  cites Zhou et al., 2017

In the paper

“GluA1 S845 dephosphorylation is critical for hippocampal LTD, as the GluA1 S845A mutation results in impaired LTD (Lee et al., 2003, Lee et al., 2010), indicating that the induction of LTD requires PKA phosphorylation of GluA1 even though receptors are eventually dephosphorylated (Huganir and Nicoll, 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Lee et al., 2003 source
• ?Not checked — no full text of the sourcecites Lee et al., 2010 source

In the paper

“Again, these findings suggest that synaptic plasticity is modulated by regulatory elements with the AMPAR C-tails, but this regulation is circumvented in the absence of AMPAR subunits.”

In the paper

“NMDAR-LTD can be rescued in the GluA1C2KI/GluA2C1KI double mutants, showing that the GluA2 C-tail is both necessary and sufficient for hippocampal NMDAR-LTD.”

What the sources say

• ?Not matched

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

  cites Zhou et al., 2017

In the paper

“During synaptic plasticity, the number of PSD slots may be altered, and/or the affinity of PSD slots for AMPARs might be changed, such that AMPARs can accumulate in the PSD during LTP and are removed during LTD (Figure 2).”

In the paper

“In the plane of the plasma membrane, AMPARs are highly mobile but become trapped in PSD slots (Opazo et al., 2012).”

What the sources say

• ?Not checked — no full text of the sourcecites Opazo et al., 2012 source