The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index; 16 of the 31 sources its claims cite were checked for support.
The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory
Open accessAbstract
UNLABELLED: MicroRNAs (miRNAs) are small, noncoding RNAs that posttranscriptionally regulate gene expression in many tissues. Although a number of brain-enriched miRNAs have been identified, only a few specific miRNAs have been revealed as critical regulators of synaptic plasticity, learning, and memory. miR-9-5p/3p are brain-enriched miRNAs known to regulate development and their changes have been implicated in several neurological disorders, yet their role in mature neurons in mice is largely unknown. Here, we report that inhibition of miR-9-3p, but not miR-9-5p, impaired hippocampal long-term potentiation (LTP) without affecting basal synaptic transmission. Moreover, inhibition of miR-9-3p in the hippocampus resulted in learning and memory deficits. Furthermore, miR-9-3p inhibition increased the expression of the LTP-related genes Dmd and SAP97, the expression levels of which are negatively correlated with LTP. These results suggest that miR-9-3p-mediated gene regulation plays important roles in synaptic plasticity and hippocampus-dependent memory. SIGNIFICANCE STATEMENT: Despite the abundant expression of the brain-specific microRNA miR-9-5p/3p in both proliferating and postmitotic neurons, most functional studies have focused on their role in neuronal development. Here, we examined the role of miR-9-5p/3p in adult brain and found that miR-9-3p, but not miR-9-5p, has a critical role in hippocampal synaptic plasticity and memory. Moreover, we identified in vivo binding targets of miR-9-3p that are involved in the regulation of long-term potentiation. Our study provides the very first evidence for the critical role of miR-9-3p in synaptic plasticity and memory in the adult mouse.
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Written from the paper’s full text.
TL;DR
Inhibition of the brain-enriched microRNA miR-9-3p, but not miR-9-5p, impairs hippocampal long-term potentiation (LTP) and hippocampus-dependent memory in mice. miR-9-3p acts at least partly by suppressing LTP-related genes Dmd and SAP97, whose increased expression correlates with impaired LTP.
Key findings
- miR-9-3p inhibition reduced theta-burst LTP at SC-CA1 synapses (last 5 min EPSC amplitude: control n=6 cells/3 mice; miR-9-3p n=9 cells/6 mice; naive n=7 cells/5 mice; one-way ANOVA F(2,19)=9.514, p=0.0014; Tukey control vs miR-9-3p and miR-9-3p vs naive, p<0.01), whereas miR-9-5p inhibition did not affect LTP (control n=12 cells/7 mice; miR-9-5p n=14 cells/6 mice; t(24)=0.8454, p=0.4062).
- miR-9-3p inhibition did not significantly affect LTD (t(14)=0.6813, p=0.5068), basal synaptic transmission, membrane excitability, sEPSCs/sIPSCs/mEPSCs/mIPSCs, or NMDA receptor-mediated EPSCs.
- miR-9-3p sponge-expressing mice showed impaired hippocampus-dependent memory: Morris water maze probe test (sponge × quadrant F(3,68)=4.44, p=0.0066; target quadrant control vs miR-9-3p p<0.05), object location memory (control t(7)=4.069, p=0.0048; miR-9-3p t(8)=0.9769, p=0.3572), and trace fear conditioning (last 4 test sessions t(6)=2.998, p=0.0241), without altered anxiety or locomotor activity.
- miR-9-3p inhibition increased hippocampal protein levels of Dmd (control 100.0±14.0%, n=7 hippocampi; miR-9-3p 156.2±14.9%, n=8; t(13)=2.724, p=0.0173) and SAP97 (control 100.0±1.2%, n=5; miR-9-3p 125.2±7.8%, n=4; t(7)=3.606, p=0.0087), while miR-9-5p inhibition did not alter either.
Methods
- Male C57BL/6N mice were used; AAV vectors expressing EGFP-tagged miR-9-3p, miR-9-5p, or control sponges under the human synapsin promoter were stereotaxically injected into dorsal CA1.
- Electrophysiology used whole-cell patch-clamp recordings in acute hippocampal slices from 4- to 5-week-old mice; behavior used 8-week-old mice in Morris water maze, object location memory, trace fear conditioning, open-field, and elevated zero maze tasks.
- Molecular validation combined TargetScan/Ingenuity Pathway Analysis target prediction, luciferase reporter assays with wild-type or mutated 3′ UTRs, and Western blots from CA1 regions expressing EGFP.
Limitations
- The paper states that LTP was induced by theta-burst stimulation with relatively short intervals, which may not be sensitive to protein synthesis and PKA inhibitors; whether miR-9-3p also regulates the protein-synthesis-dependent form of LTP remains to be determined.
- The paper notes that SAP97 was increased by miR-9-3p inhibition but no changes in excitatory synaptic transmission were detected, consistent with prior work in mature neurons.
- Evident from the text: all experiments used male mice, so sex differences are not addressed; in vivo target validation focused on Dmd and SAP97 among seven candidate genes, leaving the other candidates unvalidated in vivo.
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Claims the paper makes
15 Own result · 11 Own interpretation · 8 Partly supported · 4 No full text of the sources · 3 Supported · 3 Own method · 1 Sources not found · 1 Not checked yet · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“miR-9-3p was shown to control the transition from neural progenitor to postmitotic neurons by switching the chromatin remodeling complexes from neural-progenitor-specific BAF (npBAF) to neuron-specific BAF.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Partly supportedcites Yoo et al., 2009 sourceExperimental — accuracy not yet measured
The paper’s Abstract describes an npBAF-to-nBAF switch during the transition to post-mitotic neurons and attributes repression of BAF53a to miR-9* together with miR-124. It does not establish that miR-9-3p alone controls the transition; moreover, progenitors expressing both microRNAs did not show evidence of precocious neuronal differentiation. The copy uses the name miR-9*, not miR-9-3p. (LLM, conf=0.90)
- Partly supportedcites Yoo et al., 2011 sourceExperimental — accuracy not yet measured
The paper’s opening passage describes miR-9* and miR-124 jointly repressing an npBAF subunit as neural progenitors approach mitotic exit, followed by incorporation of neuron-specific nBAF subunits. It does not establish that miR-9-3p alone controls this transition; the paper discusses the two microRNAs together. The indexed copy provides no page number. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Interestingly, the miR-9-3p sponge had no effect on dendritic growth of cultured neurons (Giusti et al., 2014)”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Supportedcites Giusti et al., 2014 source
In Results, “MiR-9 regulates dendritic development in primary neuronal cultures” (page not provided), the authors report that sponges directed to miR-9*—the strand referred to here as miR-9-3p—had no effect on dendritic growth in cultured mouse hippocampal neurons. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“SAP97 overexpression impaired LTP (Nakagawa et al., 2004;Li et al., 2011).”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Supportedcites Nakagawa et al., 2004 source
In “LTP Occlusion by SAP97” (Figure 7; page unavailable in our copy), neurons expressing wild-type SAP97 showed much smaller LTP responses than untransfected neurons. The paper describes this as inhibition or occlusion of LTP by SAP97. (LLM, conf=0.93)
- Not matchedcites Li et al., 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, suppressing miR-9-3p activity in postmitotic neurons induced the expression of BAF53a, which is an npBAF (Yoo et al., 2009;Yoo et al., 2011)”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Partly supportedcites Yoo et al., 2009 sourceExperimental — accuracy not yet measured
The paper reports that disrupting miRNA binding sites allowed BAF53a expression to persist in neurons, and that REST expression reactivated BAF53a in postmitotic neurons. But its experiments implicate miR-9* together with miR-124; mutating the miR-9* sites alone did not abolish repression. It therefore does not establish that suppressing miR-9-3p alone induces BAF53a expression. (LLM, conf=0.86)
- Partly supportedcites Yoo et al., 2011 sourceExperimental — accuracy not yet measured
The paper’s Abstract states that miR-9* and miR-124 repress BAF53a near mitotic exit, and that BAF53a is then replaced in postmitotic neurons. It does not report that suppressing miR-9-3p activity in postmitotic neurons induced BAF53a expression; its reported repression experiment used human fibroblasts. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Object location memory was significantly impaired in the miR-9-3p sponge group”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Luciferase assay showing that the miR-9-3p sponge specifically suppresses the activity of miR-9-3p”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
boosteddirectn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, we showed that miR-9-3p, but not miR-9-5p, suppresses the expression of the well known LTP-related genes Dmd and SAP97.”
- Also stated in: § Discussion · plain
“The SAP97 protein level was significantly increased in hippocampi overexpressing the miR-9-3p sponge”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“confirmed that miR-9-3p is critical for LTP, but not for LTD induction.”
- Also stated in: § Discussion · plain
“Theta-burst LTP recordings were significantly impaired in miR-9-3psponge-expressingneurons.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
boosteddirectn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AAV-miR-9-3p sponge-expressing mice showed impaired spatial memory in the Morris water maze test”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“confirmed that miR-9-3p is critical for LTP, but not for LTD induction.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 13
- It may state two separate claims as one. 7
- The quote only partly states this claim. 1
Every source the paper cites for this claim was checked and supports it.
In the paper
“Recently, Giusti et al. (2014) showed that inhibition of miR-9-5p using sponge technique impairs dendritic growth and excitatory synaptic transmission.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Supportedcites Giusti et al., 2014 source
The Results section reports that miR-9 sponge expression reduced dendritic length and complexity in hippocampal neurons and mice. It also reports significantly reduced synaptic transmission at Schaffer collateral–CA1 synapses and reduced excitatory postsynaptic currents in sponge-expressing mice. The paper calls the inhibited strand miR-9 rather than miR-9-5p and distinguishes it from miR-9*. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“whereas others have shown that overexpressing SAP97 has no effect (Schnell et al., 2002;Schlu ¨ter et al., 2006).”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Supportedcites Schnell et al., 2002 source
The section ‘AMPAR Recruitment to Synapses Involves Synaptic PDZ Interactions’ reports that overexpressed SAP97 had no significant effect on either AMPAR- or NMDAR-mediated EPSCs. Those synaptic-current measurements support the cited claim about synaptic transmission. (LLM, conf=0.94)
- Not matchedcites Schlüter et al., 2006
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the miR-9 level was shown to be decreased in the postmortem brains of Huntington's disease patients (Packer et al., 2008)”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Supportedcites Packer et al., 2008 source
The Results section (‘miRNA expression changes with HD progression’) reports that miR-9 was significantly diminished with increasing Huntington’s disease grade in patient BA4 cortex. The Human tissues section identifies the samples as postmortem brain tissue, supporting the claim as stated. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“It is interesting that the expression levels of Dmd and SAP97 have been shown to be negatively correlated with the LTP level.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Not checked — no full text of the sourcecites Vaillend et al., 2004 source
- Partly supportedcites Nakagawa et al., 2004 sourceExperimental — accuracy not yet measured
The “LTP Occlusion by SAP97” section (page unavailable) reports that neurons expressing wild-type or L14G-SAP97 showed smaller LTP responses than untransfected neurons. This supports a limited SAP97–LTP relationship, but the paper does not report a correlation between expression levels and LTP or address Dmd. (LLM, conf=0.86)
- Not matchedcites Li et al., 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The induction of PKA-sensitive LTP requires multiple episodes of stimuli with proper interepisode intervals (Woo et al., 2003;Kim et al., 2010;Park et al., 2014;Park et al., 2016).”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Partly supportedcites Woo et al., 2003 sourceExperimental — accuracy not yet measured
The experimental protocol (Figure 1) used four bursts, and the Discussion reports that their temporal spacing determines whether the resulting LTP is PKA-dependent. But the study kept the number of bursts fixed, so it does not establish that multiple stimulation episodes are required for all PKA-sensitive LTP. (LLM, conf=0.86)
- Supportedcites Kim et al., 2010 source
The Introduction describes late-phase LTP induced by four stimulation trains and says their spacing determines whether it requires PKA. The Results (Experimental test of critical temporal interval) show that four trains spaced 80 seconds apart induced PKA-dependent LTP, whereas trains spaced 40 seconds apart induced PKA-independent LTP. (LLM, conf=0.88)
- Not matchedcites Park et al., 2014
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“SAP97 is the only member of PSD-95-like membrane associated guanylate kinases (PSD-MAGUKs) that binds directly to the C-terminus of GluA1 and is involved in AMPA receptor (AMPAR) trafficking (Leonard et al., 1998;Cai et al., 2002).”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Partly supportedcites Leonard et al., 1998 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports direct binding between SAP97 and the GluR1 (GluA1) C-terminus, but compares SAP97 with SAP90/PSD-95 and SAP102 rather than establishing that it is the only PSD-MAGUK capable of binding. The paper suggests SAP97 may help localize AMPA receptors at synapses; it does not demonstrate a role in AMPAR trafficking. (LLM, conf=0.88)
- Partly supportedcites Cai et al., 2002 sourceExperimental — accuracy not yet measured
The Results (page not provided) show that the GluR-A/GluA1 C-terminus binds SAP97, while the tested PDZ domains of PSD-93, PSD-95, and SAP102 do not. The paper does not establish that SAP97 is involved in AMPAR trafficking; it says the physiological functions of these interactions remain unclear. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The effects of SAP97 overexpression on synaptic transmission seem to be influenced by many factors, such as isoforms of SAP97 (Schlu ¨ter et al., 2006;Waites et al., 2009), compensation with other PSD-MAGUKs (Schlu ¨ter et al., 2006;Howard et al., 2010), or matureness of synapse (Howard et al., 2010).”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Not matchedcites Schlüter et al., 2006
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Waites et al., 2009 source
Waites et al. is cited for the SAP97-isoform part of the sentence; the other factors are assigned to other citations. In Results, the paper reports that αSAP97 overexpression increased, while βSAP97 overexpression decreased, AMPAR-mediated EPSC amplitudes in dissociated hippocampal neurons. The indexed passage has no page number. (LLM, conf=0.94)
- Supportedcites Howard et al., 2010 source
The section on acute SAP97β overexpression reports no increase in synaptic currents in mature wild-type neurons, but compensation for AMPAR-current deficits in PSD-93/-95 double-knockout neurons. The paper also reports enhanced transmission with overexpression in immature neurons, supporting the cited point about synapse maturity. The isoform point is attributed to other citations in the citing sentence. (LLM, conf=0.93)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Inhibition of miR-9-3p activity impairs hippocampus-dependent memories.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Basal anxiety level and locomotor activity were intact in both AAV-sponge groups.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that miR-9-3p is involved in LTP induction, very likely through regulating AMPAR trafficking.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“however, its role in excitatory synaptic transmission and AMPAR trafficking is controversial.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dmd and SAP97 are novel targets of miR-9-3p.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that miR-9-3p is critical for neuronal differentiation.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“However, miR-9-5p and miR-9-3p are abundantly expressed, not only in neural progenitors, but also in postmitotic neurons (Yuva-Aydemir et al., 2011;Liu et al., 2012).”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our finding showing downregulation of Dmd by miR-9-3p may provide new insights for the development of treatments for cognitive impairment in DMD patients.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“The miR-9-5p/3p gene is ancient in evolution and well conserved.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Not checked — no full text of the sourcecites Wheeler et al., 2009 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Nash et al. (2010) showed that the SAP97-myosin VI complex plays a critical role in trafficking of AMPARs to synapses”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
What the sources say
- Not matchedcites Nash et al., 2010
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results demonstrate that miR-9-3p is critically involved in hippocampal LTP and long-term memory.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“MiR-9-5p is known to be involved in neurogenesis, axon development, differentiation, and proliferation of neural progenitor cells27.”
From A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase (2025) · cites this paper as [27]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“miR-7 regulates neuronal death and glutamatergic signaling 40,41 ; miR-137 is critical for neural development 42 ; miR-935 and miR-129-2-3p are both elevated in epileptic brains and plasma 43 .”
From Human brain microRNAs exhibit cell-type specificity and age dependence (2026) · cites this paper as [42]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Discussion
“F, Hippocampal LTD was comparable between control and miR-9-5p sponge-expressing neurons.”
§ The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory > Inhibition of miR-9-3p impairs LTP LTP at the hippocampal Shaffer collateral-CA1 (SC-CA1)
“In addition to LTP, we also investigated whether miR-9-3p sponge expression affects LTD in the CA3-CA1 synapse of the hippocampus (Fig. 1F).”
Citations
Cites
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400
MicroRNAs: small RNAs with a big role in gene regulation
He, L., & Hannon, G. J. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1379 · Cited by 7,118
Synaptic Plasticity and Memory: An Evaluation of the Hypothesis
Martin, S. J., Grimwood, P. D., & Morris, R. G. M. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.649 · Cited by 2,794
Collingridge, G. L., Kehl, S. J., & McLennan, H. (1983) · The Journal of Physiology · doi:10.1113/jphysiol.1983.sp014478 · Cited by 2,413
MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells
Ebert, M. S., Neilson, J. R., & Sharp, P. A. (2007) · Nature Methods · doi:10.1038/nmeth1079 · Cited by 2,108
A brain-specific microRNA regulates dendritic spine development
Schratt, G. M., Tuebing, F., Nigh, E. A., Kane, C. G., Sabatini, M. E., Kiebler, M., & Greenberg, M. E. (2006) · Nature · doi:10.1038/nature04367 · Cited by 1,786
The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.
Tsien, J. Z., Huerta, P. T., & Tonegawa, S. (1996) · Cell · doi:10.1016/s0092-8674(00)81827-9 · Cited by 1,782
Cited by
Sorted by citations
Wang, J., Li, L., Zhang, Z., Zhang, X., Zhu, Y., Zhang, C., & Bi, Y. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.08.004 · Cited by 266
How the epigenome integrates information and reshapes the synapse
Campbell, R. R., & Wood, M. A. (2019) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0121-9 · Cited by 185
Ku, T., Li, B., Gao, R., Zhang, Y., Yan, W., Ji, X., Li, G., & Sang, N. (2017) · Particle and Fibre Toxicology · doi:10.1186/s12989-017-0215-3 · Cited by 159
DNA nanotechnology approaches for microRNA detection and diagnosis
Chandrasekaran, A. R., Punnoose, J. A., Zhou, L., Dey, P., Dey, B. K., & Halvorsen, K. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz580 · Cited by 150
Rbfox1 Regulates Synaptic Transmission through the Inhibitory Neuron-Specific vSNARE Vamp1
Vuong, C. K., Wei, W., Lee, J.-A., Lin, C.-H., Damianov, A., de la Torre-Ubieta, L., Halabi, R., Otis, K. O., Martin, K. C., O’Dell, T. J., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.03.008 · Cited by 102
Self-citation
Metadata
- Authors
- Sim, S.-E., Lim, C.-S., Kim, J.-I., Seo, D., Chun, H., Yu, N.-K., Lee, J., Kang, S. J., Ko, H.-G., Choi, J.-H., Kim, T., Jang, E.-H., Han, J., Bak, M. S., Park, J.-E., Jang, D.-J., Baek, D., Lee, Y.-S., & Kaang, B.-K.
- Affiliations
- Department of Biological Sciences (RU)
- Institute for Basic Science (KR)
- Chung-Ang University (KR)
- Kyungpook National University (KR)
- Seoul National University (KR)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2016-08-17
- Volume
- 36
- Issue
- 33
- Pages
- 8641-8652
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6601897
- OpenAlex
- W2510924509
- Semantic Scholar
- f4ec49a6625afe4ee944887e877ccac25d3cd6bf
- Cited by
- 116
- References
- 67
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 18 · 2023: 11 · 2022: 16 · 2021: 10 · 2020: 15 · 2019: 15 · 2018: 8 · 2017: 7
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Funders
- National Research Foundation
- National Research Foundation of Korea (2012R1A3A1050385)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- miR-9-3p, miR-9-5p, microRNA, synaptic plasticity, long-term potentiation, hippocampus, learning and memory, DMD, SAP97, post-transcriptional regulation, adult neurons, miRNA target genes
- MeSH terms
- Discs Large Homolog 1 Protein, Animals, Conditioning, Psychological, Exploratory Behavior, Fear, Hippocampus, Humans, Male, Membrane Proteins, Mice, Inbred C57BL, Neuronal Plasticity, Transduction, Genetic, Dystrophin, Synapsins, Maze Learning, Receptors, CXCR4, Recognition, Psychology, MicroRNAs, Green Fluorescent Proteins, Mice, Guanylate Kinases, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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