The DOI matches its Crossref record; 68 of the 84 references it cites were found in a registry or an index, and 16 are not checked yet; none of the 39 sources its claims cite is checked for support yet.
Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice
Open accessAbstract
Abnormal sensory responses associated with Fragile X Syndrome (FXS) and autism spectrum disorders include hypersensitivity and impaired habituation to repeated stimuli. Similar sensory deficits are also observed in adult Fmr1 knock-out (KO) mice and are reversed by genetic deletion of Matrix Metalloproteinase-9 (MMP-9) through yet unknown mechanisms. Here we present new evidence that impaired development of parvalbumin (PV)-expressing inhibitory interneurons may underlie hyper-responsiveness in auditory cortex of Fmr1 KO mice via MMP-9-dependent regulation of perineuronal nets (PNNs). First, we found that PV cell development and PNN formation around GABAergic interneurons were impaired in developing auditory cortex of Fmr1 KO mice. Second, MMP-9 levels were elevated in P12-P18 auditory cortex of Fmr1 KO mice and genetic reduction of MMP-9 to WT levels restored the formation of PNNs around PV cells. Third, in vivo single-unit recordings from auditory cortex neurons showed enhanced spontaneous and sound-driven responses in developing Fmr1 KO mice, which were normalized following genetic reduction of MMP-9. These findings indicate that elevated MMP-9 levels contribute to the development of sensory hypersensitivity by influencing formation of PNNs around PV interneurons suggesting MMP-9 as a new therapeutic target to reduce sensory deficits in FXS and potentially other autism spectrum disorders.
Checked 2026-10-06 · 16 references not checked yet
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49 Own result · 24 Not checked yet · 13 Own interpretation · 10 Own method · 1 No basis given
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
“A significant developmental increase in PV cell density was observed in both WT and Fmr1 KO auditory cortex at P21 (Table 1; age effect, P < 0.01).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > PV Cell Development is Impaired in the Developing Auditory Cortex of Fmr1 KO Mice
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, PV cell density was lower in the developing Fmr1 KO auditory cortex compared to WT (Table 1; genotype effect, P < 0.05).”
- Also stated in: § Abstract · plain
“First, we found that PV cell development and PNN formation around GABAergic interneurons were impaired in developing auditory cortex of Fmr1 KO mice.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > PV Cell Development is Impaired in the Developing Auditory Cortex of Fmr1 KO Mice
plaincorrelational- 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: § Abstract · 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
“However, a developmental increase in PV cell density was only detected in L4 but not L2/3 of WT auditory cortex (WT, P14 vs P21, P < 0.01; Fig. 1J).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > PNN Formation is Selectively Impaired Around PV Interneurons in Fmr1 KO Auditory Cortex at P21
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Third, in vivo single-unit recordings from auditory cortex neurons showed enhanced spontaneous and sound-driven responses in developing Fmr1 KO mice, which were normalized following genetic reduction of MMP-9.”
- Also stated in: § Genetic Reduction of MMP-9 Restores Auditory Cortex Response Magnitudes in Fmr1 KO Neurons to WT Levels · plain
“Responses were restored to WT levels with genetic reduction of MMP-9 levels in the Mmp9 +/-Fmr1 KO mice (Fig. 6B-D).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Genetic Reduction of MMP-9 Restores Auditory Cortex Response Magnitudes in Fmr1 KO Neurons to WT Levels · 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
“While PNN labeling was also detected around GAD65/67 negative cells (presumably excitatory neurons; arrowheads in Fig. 2C,D), there were no genotype differences in the density of PNN-containing cells lacking GAD65/67, indicating that impaired PNN formation was specific to GABAergic interneurons at P21.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Reduced PNN Formation Around GABAergic Interneurons in L4 Fmr1 KO Auditory Cortex at P21
plain- Asserted: passes — The authors put it forward as true.
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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
“PV cell density was lower in L4 Fmr1 KO auditory cortex compared to WT at all ages (genotype effect, P < 0.05; Fig. 1J).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > PNN Formation is Selectively Impaired Around PV Interneurons in Fmr1 KO Auditory Cortex at P21
plain- 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.
In the paper
“However, at P21, Fmr1 KO mice showed increased response magnitude across the entire 200 ms recording window compared to WT, as seen previously in adults (Rotschafer and Razak 2013; Fmr1 KO vs. WT, P < 0.01; Fig. 5E).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Response Magnitudes are Increased in Developing Auditory Cortex of Fmr1 KO Mice
What the sources say
- Not checked yetcites Rotschafer and Razak 2013
plaincorrelational- 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
“Although there was a delay in PNN development in Fmr1 KO auditory cortex, overall density of PNN-containing cells was not significantly different between genotypes.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > PV Cell Development is Impaired in the Developing Auditory Cortex of Fmr1 KO Mice
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that at P21 PNN formation was selectively impaired around PV cells in Fmr1 KO auditory cortex compared to WT in both L2/3 (P < 0.01) and L4 (P < 0.0001; Fig. 1L).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > PNN Formation is Selectively Impaired Around PV Interneurons in Fmr1 KO Auditory Cortex at P21
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First, we found that PV cell development and PNN formation around GABAergic interneurons were impaired in developing auditory cortex of Fmr1 KO mice.”
- Also stated in: § PNN Formation is Selectively Impaired Around PV Interneurons in Fmr1 KO Auditory Cortex at P21 · plain
“We found that at P21 PNN formation was selectively impaired around PV cells in Fmr1 KO auditory cortex compared to WT in both L2/3 (P < 0.01) and L4 (P < 0.0001; Fig. 1L).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Abstract
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.
- Also stated in: § PNN Formation is Selectively Impaired Around PV Interneurons in Fmr1 KO Auditory Cortex at P21 · plain
- It may state two separate claims as one. 43
- Probably not a substantial claim. 17
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In WT auditory cortex, MMP-9 levels decreased at P12 and remained low at P18 (Fig. 3A,B; effect of age P < 0.001), during the period of active PNN formation around PV cells and maturation of auditory cortex.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > MMP-9 Levels are Higher in the Developing Auditory Cortex of Fmr1 KO Mice
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 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
“Fmr1 KO mice also exhibited age-related increase in spontaneous activity from P14 to P21 and more spontaneous activity in P21 Fmr1 KO auditory cortex compared to WT (Fmr1 KO mice P14-> P21 P < 0.01, Fmr1 KO vs. WT, P < 0.0001; Fig 5F).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Response Magnitudes are Increased in Developing Auditory Cortex of Fmr1 KO Mice
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The spontaneous activity was also significantly higher in the Fmr1 KO mice compared to WT (Fmr1 KO vs. WT, P < 0.0001; Fig. 6E) and was restored to WT levels with MMP-9 reduction (Fmr1 KO vs. Mmp9 +/-Fmr1 KO, P < 0.0001; Fig. 6E).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Genetic Reduction of MMP-9 Restores Auditory Cortex Response Magnitudes in Fmr1 KO Neurons to WT Levels
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the percentage of PV cells containing PNN was restored to WT levels in layer 4 of Mmp9 +/-Fmr1 KO auditory cortex at P21 and was significantly higher than in Fmr1 KO (P < 0.001; Fig. 4G).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > MMP-9 Reduction Promotes PNN Formation Around PV Interneurons in Layer 4 of Fmr1 KO Auditory Cortex
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“PNN density was significantly higher in layer 4 of Mmp9 +/-Fmr1 KO auditory cortex than in Fmr1 KO at P21 (P < 0.0001; Fig. 4E), even exceeding WT levels (P < 0.01; Fig. 4E).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > MMP-9 Reduction Promotes PNN Formation Around PV Interneurons in Layer 4 of Fmr1 KO Auditory Cortex
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“PNN density was lower in L4 Fmr1 KO auditory cortex compared to WT mice at P14 (P < 0.0001) and did not reach WT levels until P30 (Fig. 1K).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > PNN Formation is Selectively Impaired Around PV Interneurons in Fmr1 KO Auditory Cortex at P21
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“PNN cell density was reduced in Fmr1 KO mice (*P < 0.05) but was significantly higher in Mmp9 +/-Fmr1 KO mice compared to KO (****P < 0.001).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MMP-2 levels also showed a developmental down-regulation from P3 to P18 (Fig. 4C; P < 0.05) but levels were similar between WT and Fmr1 KO mice at all ages (Fig. 4C; P = n.s.).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plainn = 4- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“PNN/PV cell density was reduced in Fmr1 KO compared to WT cortex (****P < 0.0001), but was significantly higher in Mmp9 +/-Fmr1 KO compared to KO (**P < 0.01).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fmr1 KO mice showed reduced percentage of PV cells with PNNs but not after MMP-9 reduction in Mmp9 +/-Fmr1 KO mice (WT vs. Fmr1 KO, ****P < 0.0001; Mmp9 +/-Fmr1 KO vs. Fmr1 KO, ***P < 0.01).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was a developmental increase in GAD-negative cells enwrapped with PNNs (P21 vs. P30; **P < 0.01), but there were no genotype-specific differences.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plainn = 3- 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.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Spontaneous activity was also significantly higher in Fmr1 KO auditory cortex at P21 but not P14.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plainn = 91- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed a selective loss of PNNs around PV-positive GABAergic interneurons at P21, with no differences observed in PNN expression around PV-negative neurons at P21.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Analysis shows increased spikes/stimulus in the ongoing response (C) but not the first 50 ms onset response (B) in Fmr1 KO auditory cortex as compared to WT at P21 but not P14 (P21 WT vs. Fmr1 KO, **P < 0.01).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plainn = 89- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of MMP-9 peak at P7 and decrease with age during auditory cortex development in WT mice; however compared to WT levels MMP-9 levels are elevated in Fmr1 KO mice at all ages (P < 0.01).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we report that MMP-9 levels are also elevated during a developmental sensitive window in Fmr1 KO auditory cortex, whereas genetic reduction of MMP-9 in Fmr1 KO mice rescues observed PNN deficits and restores response magnitudes and spontaneous activity to WT levels.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, response magnitude increases in Fmr1 KO auditory cortex with age but not in WT (Fmr1 KO P14-> P21, P < 0.001).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plaindirectn = 85- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of MMP-9 were significantly higher in Fmr1 KO (*P < 0.05) but not MMP-9 +/-Fmr1 KO auditory cortex as compared to WT, whereas MMP-9 levels were significantly lower in MMP-9 +/-Fmr1 KO auditory cortex as compared to Fmr1 KO (**P < 0.01).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plainn = 9- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Our previous studies showed hyperexcitable auditory cortical responses (Rotschafer and Razak 2013) and impaired habituation to repeated sounds in adult Fmr1 KO mice (Lovelace et al. 2016), suggesting impaired E/I balance.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
- Not checked yetcites Rotschafer and Razak 2013
- Not checked yetcites Lovelace et al. 2016 source
hedgedcorrelational- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“MMP-9 deletion reverses several FXS phenotypes in Fmr1 KO mice (Sidhu et al. 2014), including impaired auditory response habituation (Lovelace et al. 2016).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Nevertheless, the precise boundary between primary auditory cortex (A1) and anterior auditory field (AAF) of the mouse auditory cortex cannot be clearly established.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Immunohistochemistry and Image Analysis
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“converted to a TIFF file, encoded for blind analysis, and analyzed using Image J.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Immunohistochemistry and Image Analysis
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Auditory cortex was identified using hippocampal landmarks.This method has been previously validated using tonotopic mapping and dye injection (Martin del Campo et al. 2012) and comparison with the Paxinos mouse atlas and other publications on mouse auditory cortex (Anderson et al. 2009).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Immunohistochemistry and Image Analysis
What the sources say
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In the paper
“Matrix Metalloproteinase-9 (MMP-9) is a secreted endopeptidase, which regulates PNN formation and organization by cleaving ECM components (Ethell and Ethell 2007).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Introduction
What the sources say
- Not checked yetcites Ethell and Ethell 2007
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Abnormal sensory responses associated with Fragile X Syndrome (FXS) and autism spectrum disorders include hypersensitivity and impaired habituation to repeated stimuli.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Abstract
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In the paper
“These data indicate that responses become abnormally high between P14 and P21 Fmr1 KO auditory cortex, a time window during which the PNNs mature around PV interneurons.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Response Magnitudes are Increased in Developing Auditory Cortex of Fmr1 KO Mice
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In the paper
“These data are also consistent with altered PV cell function in other autism mouse models (Gogolla et al. 2009).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
- Not checked yetcites Gogolla et al. 2009 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“All images were acquired under identical conditions.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Immunohistochemistry and Image Analysis
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Similar sensory deficits are also observed in adult Fmr1 knock-out (KO) mice and are reversed by genetic deletion of Matrix Metalloproteinase-9 (MMP-9) through yet unknown mechanisms.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Abstract
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Normal development of fast-spiking parvalbumin (PV)-positive inhibitory interneurons is implicated in shaping”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Introduction
What the sources say
- Not checked yetcites Hensch 2005 source
- Not checked yetcites Jeevakumar and Kroener 2016
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In the paper
“Thus the loss of PNN around PV cells may lead to impaired maturation, survival and/or reduced excitability of PV neurons and overall loss of inhibition in the network leading to FXSrelated sensory hypersensitivity.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“PNNs enwrap both inhibitory and excitatory neurons (Carulli et al. 2006)”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
- Not checked yetcites Carulli et al. 2006 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Genotypes were confirmed by PCR analysis of genomic DNA isolated from mouse tails.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Mice
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In the paper
“the distribution of neuron depths did not differ between WT and KO at P14, and WT, KO, and Mmp9 +/-Fmr1 KO mice at P21 (P = n.s.; Chisquare: Depth × Genotype).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > In Vivo Extracellular Electrophysiology
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In the paper
“PNNs also regulate PV cell maturation via internalization of homeoprotein Otx2, which is needed for transcription, normal PV development and critical period plasticity in developing visual cortex (Sugiyama et al. 2008).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
- Not checked yetcites Sugiyama et al. 2008 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. 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
“Elevated MMP-9 levels in Fmr1 KO auditory cortex are most likely responsible for the developmental delay in PNN formation around PV cells during auditory cortex development and is at least partially responsible for auditory processing deficits.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“FMRP may regulate PV cell fate through translational control of transcription factors necessary for GABAergic neuron differentiation (reviewed in Sultan et al. 2013).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
- Not checked yetcites Sultan et al. 2013 source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“PNNs regulate survival (Morawski et al. 2004(Morawski et al. , 2015;;Cabungcal et al. 2013) and excitability of PV interneurons (Dityatev et al. 2007;Carulli et al. 2010;Balmer 2016), and stabilization of sensory circuits (Pizzorusso et al. 2002;McRae et al. 2007).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Genetic deletion of MMP-9 rescues several other FXS phenotypes, including improper dendritic spine maturation, enhanced mGluR5-dependent-LTD, abnormal social behavior and macroorchidism (Sidhu et al. 2014)”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
plaindirect- 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.
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
“Auditory hypersensitivity developed between P14 and P21, which coincides with a critical window for E/I balance maturation and PNN formation in the auditory cortex.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The frequency response of the sound delivery system, assessed with a 1 inch Bruel and Kjaer microphone and measuring amplifier, was flat within ± 4 dB between 5 and 40 kHz.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > In Vivo Extracellular Electrophysiology
plain- 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.
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
“While delayed PNN formation may contribute to enhanced excitability in P21 Fmr1 KO mice, this does not explain impaired PV cell development that occurs during early PNN formation at P14.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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
“Fmr1 KO neurons exhibit increased response magnitudes and spontaneous activity and PV/PNN deficits during this developmental window that coincides with the maturation of cortical inhibition.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“MMP-9 levels are elevated in FXS human brains and the hippocampus of Fmr1 KO mice (Dziembowska et al., 2013;Sidhu et al. 2014;Gkogkas et al. 2014).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, we found a significant reduction in PV expression and PV/PNN colocalization in MMP-9 -/mice (not shown), which is consistent with MMP-9 role in neurodevelopment (reviewed in Reinhard et al. 2015), suggesting that too much or too little MMP-9 would affect PV cell development.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
- Not checked yetcites Reinhard et al. 2015 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Here age-matched (P13-16 and P19-23) male WT, Fmr1 KO, Mmp9 +/-Fmr1 mice were anesthetized with a combination of 1 g/kg urethane and 20 mg/kg xylazine.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > In Vivo Extracellular Electrophysiology
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. 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
“The abnormally high MMP-9 levels, altered PV/PNN development and increased responses that we observed in Fmr1 KO auditory cortex occur during a critical window of auditory cortex development in mice.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Another major finding presented here is that developmental delay in PNN formation in Fmr1 KO auditory cortex may be attributed to elevated MMP-9 levels, as genetic reduction in MMP-9 levels was able to reverse abnormal PNN formation around PV cells and to restore auditory response magnitude at P21.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Chondroitinase ABC, an enzyme that cleaves PNN proteoglycans, reduces GABA A inhibitory postsynaptic currents (Liu et al. 2013) and reduces excitability of PV fast-spiking cortical interneurons (Balmer 2016).”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
What the sources say
- Not checked yetcites Liu et al. 2013
- Not checked yetcites Balmer 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Taken together, these data indicate that increased single neuron hyperexcitability in Fmr1 KO auditory cortex may arise from delayed maturation of PV neurons, which can occur with disruption of PNNs.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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
“Therefore, hypersensitive neural circuits are not present around the time of hearing onset in the Fmr1 KO mice, but develop between P14 and P21 suggesting a window for potential treatment of sensory hypersensitivity.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
hedged- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All procedures were approved by the Institutional Animal Care and Use Committee at the University of California, Riverside and carried out in accordance with NIH”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Mice
plain- 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. The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Mmp9 +/-Fmr1 KO brain samples were collected and analyzed together with experimentally matched WT and KO groups.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Toe pinch reflex was monitored to ensure sufficient anesthesia levels and maintained with supplemental doses of urethane and xylazine.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > In Vivo Extracellular Electrophysiology
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The role of ECM in cortical plasticity has been previously reported (Pizzorusso et al. 2002;Nagy et al. 2006;McRae et al. 2007;Rivera et al. 2010)”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > 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.
The paper relies on this without support.
MMP-9 protein levels measured by gelatin zymography reflect MMP-9 enzymatic activity in vivo.
“Levels of MMP-2 and MMP-9 proteins were quantified by densitometry using Image J.”
The paper relies on this without support.
Genetic reduction of MMP-9 in Mmp9+/- Fmr1 knock-out mice does not cause compensatory changes that independently affect PNN formation or auditory responses.
“The FVB.Cg-Mmp-9 tm1Tvu /J mice were backcrossed, in-house, with Fmr1 KO mice to generate Mmp9 +/-Fmr1 KO mice, which had only 1 allele of the Mmp9 gene and reduced expression of MMP-9.”
The paper relies on this without support.
The restoration of auditory responses by MMP-9 reduction is mediated by changes in PNN formation around PV cells rather than by a direct effect of MMP-9 on neuronal excitability.
“These data implicate MMP-9 in the development of auditory cortex hyperexcitability in Fmr1 KO mice via the regulation of PNN formation around PV interneurons and provide further support for targeting MMP-9 in treatment of FXS.”
The paper relies on this without support.
Findings in mouse auditory cortex are relevant to human FXS sensory deficits.
“These findings indicate that elevated MMP-9 levels contribute to the development of sensory hypersensitivity by influencing formation of PNNs around PV interneurons suggesting MMP-9 as a new therapeutic target to reduce sensory deficits in FXS and potentially other autism spectrum disorders.”
The authors state this as an assumption.
In wild-type animals, FMRP translationally suppresses MMP-9 production.
“In WT animals, there is normal production of FMRP, which translationally suppresses MMP-9 production, resulting in normal development and maturation of PV interneurons (white) and PNNs (black) and normal neural excitability.”
The authors state this as an assumption.
In Fmr1 knockout mice, loss of FMRP leads to upregulated production of MMP-9.
“Fmr1 KO results in loss of FMRP and upregulated production of MMP-9.”
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?
In the citing paper
“However, the role of PNNs in neural and network excitability is only beginning to be understood (Balmer, 2016; Murase et al., 2017; Wen et al., 2017).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Wen et al., 2017
In the citing paper
“As aggrecan has been previously identified as an MMP-9 target (Mercuri et al., 2000; Madsen et al., 2010; Rankin-Gee et al., 2015), aggrecan-rich PNNs may be unstable in the presence of MMP-9, leading to abnormal development and neural excitability (Murase et al., 2017; Wen et al., 2017).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Wen et al., 2017
In the citing paper
“Peak MMP-9 expression is observed during postnatal development and is reduced during adulthood (Bednarek et al., 2009; Reinhard et al., 2015; Wen et al., 2017).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Wen et al., 2017
In the citing paper
“We found delayed PNN development and increased MMP-9 activity levels in the developing auditory cortex of Fmr1 KO mice (Wen et al., 2017), which may lead to impaired PV cell development and reduced inhibition.”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Wen et al., 2017
In the citing paper
“We found delayed PNN development and increased MMP-9 activity levels in the developing auditory cortex of Fmr1 KO mice (Wen et al., 2017), which may lead to impaired PV cell development and reduced inhibition.”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Wen et al., 2017
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
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Gelatin Zymography
“P3, P7, P12, and P18 mice (n = 3-7 mice per group) were euthanized with isoflurane”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
“(WT N: 6, 8, 4, and 4 mice.Fmr1 KO N: 6, 8, 4, and 4 mice).”
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
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Immunohistochemistry and Image Analysis
“For each brain, an average of 5-6 slices containing auditory cortex were obtained.”
§ Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice > Discussion
“Fmr1 KO N: P14 3/22; P21 6/45; P30 7/66; *P < 0.05; **P < 0.01; ****P < 0.0001”
Citations
Cites
The mouse brain in stereotaxic coordinates
Konsman, J. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(03)00088-x · Cited by 16,796
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
Mechanisms of Gamma Oscillations
Buzsáki, G., & Wang, X.-J. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062111-150444 · Cited by 2,796
Model of autism: increased ratio of excitation/inhibition in key neural systems
Rubenstein, J. L. R., & Merzenich, M. M. (2003) · Genes, Brain and Behavior · doi:10.1034/j.1601-183x.2003.00037.x · Cited by 2,768
Parvalbumin neurons and gamma rhythms enhance cortical circuit performance
Sohal, V. S., Zhang, F., Yizhar, O., & Deisseroth, K. (2009) · Nature · doi:10.1038/nature07991 · Cited by 2,606
Driving fast-spiking cells induces gamma rhythm and controls sensory responses
Cardin, J. A., Carlén, M., Meletis, K., Knoblich, U., Zhang, F., Deisseroth, K., Tsai, L.-H., & Moore, C. I. (2009) · Nature · doi:10.1038/nature08002 · Cited by 2,603
Critical period plasticity in local cortical circuits
Hensch, T. K. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1787 · Cited by 2,323
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072
NEURONAL CIRCUITS OF THE NEOCORTEX
Douglas, R. J., & Martin, K. A. C. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144152 · Cited by 1,886
Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex
Pizzorusso, T., Medini, P., Berardi, N., Chierzi, S., Fawcett, J. W., & Maffei, L. (2002) · Science · doi:10.1126/science.1072699 · Cited by 1,679
Fragile X Genotype Characterized by an Unstable Region of DNA
Yu, S., Pritchard, M. A., Kremer, E. J., Lynch, M., Nancarrow, J. K., Baker, E. G., Holman, K., Mulley, J. C., Warren, S. T., Schlessinger, D., et al. (1991) · Science · doi:10.1126/science.252.5009.1179 · Cited by 793
FMR1 and the fragile X syndrome: Human genome epidemiology review
Crawford, D. C., Acuña, J. M., & Sherman, S. L. (2001) · Genetics in Medicine · doi:10.1097/00125817-200109000-00006 · Cited by 711
Common circuit defect of excitatory-inhibitory balance in mouse models of autism
Gogolla, N., LeBlanc, J. J., Quast, K. B., Südhof, T. C., Fagiolini, M., & Hensch, T. K. (2009) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-009-9023-x · Cited by 610
Advances in the Treatment of Fragile X Syndrome
Hagerman, R. J., Berry-Kravis, E., Kaufmann, W. E., Ono, M. Y., Tartaglia, N., Lachiewicz, A., Kronk, R., Delahunty, C., Hessl, D., Visootsak, J., et al. (2009) · Pediatrics · doi:10.1542/peds.2008-0317 · Cited by 596
Gibson, J. R., Bartley, A. F., Hays, S. A., & Huber, K. M. (2008) · Journal of Neurophysiology · doi:10.1152/jn.90752.2008 · Cited by 529
Perineuronal nets protect fast-spiking interneurons against oxidative stress
Cabungcal, J.-H., Steullet, P., Morishita, H., Kraftsik, R., Cuenod, M., Hensch, T. K., & Do, K. Q. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300454110 · Cited by 512
Matrix metalloproteinase-9 is required for hippocampal late-phase long-term potentiation and memory
Nagy, V., Bozdagi, O., Matynia, A., Balcerzyk, M., Okulski, P., Dzwonek, J., Costa, R. M., Silva, A. J., Kaczmarek, L., & Huntley, G. W. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4359-05.2006 · Cited by 499
Animals lacking link protein have attenuated perineuronal nets and persistent plasticity
Carulli, D., Pizzorusso, T., Kwok, J. C. F., Putignano, E., Poli, A., Forostyak, S., Andrews, M. R., Deepa, S. S., Glant, T. T., & Fawcett, J. W. (2010) · Brain · doi:10.1093/brain/awq145 · Cited by 495
Sugiyama, S., Di Nardo, A. A., Aizawa, S., Matsuo, I., Volovitch, M., Prochiantz, A., & Hensch, T. K. (2008) · Cell · doi:10.1016/j.cell.2008.05.054 · Cited by 491
Bilousova, T. V., Dansie, L., Ngo, M., Aye, J., Charles, J. R., Ethell, D. W., & Ethell, I. M. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.061796 · Cited by 465
Self-citationd’Ortho, M., Will, H., Atkinson, S. J., Butler, G. S., Messent, A., Gavrilović, J., Smith, B., Timpl, R., Zardi, L., & Murphy, G. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00751.x · Cited by 443
Altered Neuronal and Circuit Excitability in Fragile X Syndrome
Contractor, A., Klyachko, V. A., & Portera‐Cailliau, C. (2015) · Neuron · doi:10.1016/j.neuron.2015.06.017 · Cited by 418
Matrix metalloproteinases in brain development and remodeling: Synaptic functions and targets
Ethell, I. M., & Ethell, D. W. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21273 · Cited by 378
Self-citationDityatev, A., Brückner, G., Dityateva, G., Grosche, J., Kleene, R., & Schachner, M. (2007) · Developmental Neurobiology · doi:10.1002/dneu.20361 · Cited by 365
Disparate roles of zinc in chemical hypoxia-induced neuronal death
Kim, S., Seo, J.-W., Oh, S. B., Kim, S., Kim, I., Suh, N., & Lee, J. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00001 · Cited by 363
Fragile X mice develop sensory hyperreactivity to auditory stimuli
Chen, L., & Toth, M. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00036-7 · Cited by 345
Carulli, D., Rhodes, K. E., Brown, D. J., Bonnert, T. P., Pollack, S. J., Oliver, K., Strata, P., & Fawcett, J. W. (2006) · Journal of Comparative Neurology · doi:10.1002/cne.20822 · Cited by 341
Lensjø, K. K., Lepperød, M. E., Dick, G., Hafting, T., & Fyhn, M. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2504-16.2016 · Cited by 281
Circuit level defects in the developing neocortex of fragile X mice
Gonçalves, J. T., Anstey, J. E., Golshani, P., & Portera-Cailliau, C. (2013) · Nature Neuroscience · doi:10.1038/nn.3415 · Cited by 279
Sensory Deprivation Alters Aggrecan and Perineuronal Net Expression in the Mouse Barrel Cortex
McRae, P. A., Rocco, M. M., Kelly, G., Brumberg, J. C., & Matthews, R. T. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5425-06.2007 · Cited by 272
Epilepsy in fragile X syndrome
Berry‐Kravis, E. (2002) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2002.tb00277.x · Cited by 271
The fra(X) syndrome: Neurological, electrophysiological, and neuropathological abnormalities
Wisniewski, K. E., Segan, S. M., Miezejeski, C. M., Sersen, E. A., & Rudelli, R. D. (1991) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320380267 · Cited by 261
Epilepsy and EEG Findings in Males with Fragile X Syndrome
Musumeci, S. A., Hagerman, R. J., Ferri, R., Bosco, P., Bernardina, B. D., Tassinari, C. A., Sarro, G. D., & Elia, M. (1999) · Epilepsia · doi:10.1111/j.1528-1157.1999.tb00824.x · Cited by 250
Perineuronal nets potentially protect against oxidative stress
Morawski, M., Brückner, M. K., Riederer, P., Brückner, G., & Arendt, T. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.04.017 · Cited by 246
Selby, L., Zhang, C., & Sun, Q.-Q. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2006.11.062 · Cited by 245
Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1−/y mice
Zhang, Y., Bonnan, A., Bony, G., Férézou, I., Pietropaolo, S., Ginger, M. R., Sans, N., Rossier, J., Oostra, B. A., LeMasson, G., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3864 · Cited by 239
Auditory thalamocortical transformation: structure and function
Winer, J. A., Miller, L. M., Lee, C. C., & Schreiner, C. E. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.03.009 · Cited by 229
Metzincin proteases and their inhibitors: foes or friends in nervous system physiology?
Rivera, S., Khrestchatisky, M., Kaczmarek, L., Rosenberg, G. A., & Jaworski, D. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3467-10.2010 · Cited by 223
Perineuronal Nets Enhance the Excitability of Fast-Spiking Neurons
Balmer, T. S. (2016) · eneuro · doi:10.1523/eneuro.0112-16.2016 · Cited by 220
Reinhard, S. M., Razak, K., & Ethell, I. M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00280 · Cited by 219
Self-citationDevelopment of absolute auditory thresholds in the house mouse (Mus musculus).
Ehret, G. (1976) · PubMed · Cited by 213
Gkogkas, C. G., Khoutorsky, A., Cao, R., Jafarnejad, S. M., Prager-Khoutorsky, M., Giannakas, N., Kaminari, A., Fragkouli, A., Nader, K., Price, T. J., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.064 · Cited by 201
Complementary control of sensory adaptation by two types of cortical interneurons
Natan, R. G., Briguglio, J. J., Mwilambwe-Tshilobo, L., Jones, S. I., Aizenberg, M., Goldberg, E. M., & Geffen, M. N. (2015) · eLife · doi:10.7554/elife.09868 · Cited by 200
Sinclair, D., Oranje, B., Razak, K. A., Siegel, S. J., & Schmid, S. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.029 · Cited by 198
Self-citationEthridge, L. E., White, S. P., Mosconi, M. W., Wang, J., Byerly, M. J., & Sweeney, J. A. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.48 · Cited by 188
Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice
Pietropaolo, S., Guilleminot, A., Martin, B., D'Amato, F. R., & Crusio, W. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017073 · Cited by 178
Wang, J., Ethridge, L. E., Mosconi, M. W., White, S. P., Binder, D. K., Pedapati, E. V., Erickson, C. A., Byerly, M. J., & Sweeney, J. A. (2017) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-017-9191-z · Cited by 176
Self-citationAltered differentiation of neural stem cells in fragile X syndrome
Castrén, M., Tervonen, T., Kärkkäinen, V., Heinonen, S., Castrén, E., Larsson, K., Bakker, C. E., Oostra, B. A., & Åkerman, K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508995102 · Cited by 176
Evidence for social anxiety and impaired social cognition in a mouse model of fragile X syndrome.
McNaughton, C. H., Moon, J., Strawderman, M. S., Maclean, K. N., Evans, J., & Strupp, B. J. (2008) · Behavioral Neuroscience · doi:10.1037/0735-7044.122.2.293 · Cited by 174
High MMP-9 activity levels in fragile X syndrome are lowered by minocycline
Dziembowska, M., Pretto, D. I., Janusz, A., Kaczmarek, L., Leigh, M. J., Gabriel, N., Durbin‐Johnson, B., Hagerman, R. J., & Tassone, F. (2013) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36023 · Cited by 161
Sidhu, H., Dansie, L. E., Hickmott, P. W., Ethell, D. W., & Ethell, I. M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1162-14.2014 · Cited by 155
Self-citationFMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry
Fata, G. L., Gärtner, A., Domıńguez-Iturza, N., Dresselaers, T., Dawitz, J., Poorthuis, R. B., Averna, M., Himmelreich, U., Meredith, R. M., Achsel, T., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3870 · Cited by 151
Early developmental alterations in GABAergic protein expression in fragile X knockout mice
Adusei, D. C., Pacey, L. K. K., Chen, D., & Hampson, D. R. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.05.002 · Cited by 139
Altered auditory processing in a mouse model of fragile X syndrome
Rotschafer, S. E., & Razak, K. A. (2013) · Brain Research · doi:10.1016/j.brainres.2013.02.038 · Cited by 138
Self-citationExtracellular matrix molecules, their receptors, and secreted proteases in synaptic plasticity
Włodarczyk, J., Mukhina, I. V., Kaczmarek, L., & Dityatev, A. E. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20958 · Cited by 127
Augmentation of auditory N1 in children with fragile X syndrome.
Castrén, M., Pääkkönen, A., Tarkka, I. M., Ryynänen, M., & Partanen, J. (2003) · Brain Topography · doi:10.1023/a:1022606200636 · Cited by 123
Morphological changes in the cochlea of the mouse after the onset of hearing
Kraus, H.-J., & Aulbach-Kraus, K. (1981) · Hearing Research · doi:10.1016/0378-5955(81)90038-1 · Cited by 119
Li, L., Ji, X., Liang, F., Li, Y.-T., Xiao, Z., Tao, H. W., & Zhang, L. I. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1516-14.2014 · Cited by 117
Morawski, M., Reinert, T., Meyer-Klaucke, W., Wagner, F. E., Tröger, W., Reinert, A., Jäger, C., Brückner, G., & Arendt, T. (2015) · Scientific Reports · doi:10.1038/srep16471 · Cited by 116
Lovelace, J. W., Wen, T. H., Reinhard, S., Hsu, M. S., Sidhu, H., Ethell, I. M., Binder, D. K., & Razak, K. A. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.02.002 · Cited by 115
Self-citationImpaired inhibitory control of cortical synchronization in fragile X syndrome
Paluszkiewicz, S. M., Olmos-Serrano, J. L., Corbin, J. G., & Huntsman, M. M. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00421.2011 · Cited by 107
Saffary, R., & Xie, Z. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4854-10.2011 · Cited by 103
Rahmati, N., Veloz, M. F. V., Xu, J., Barone, S., Hamida, N. R. B., Schonewille, M., Hoebeek, F. E., Soleimani, M., & Zeeuw, C. I. D. (2016) · eNeuro · doi:10.1523/eneuro.0028-16.2016 · Cited by 96
Epilepsy and EEG findings in 18 males with fragile X syndrome
Sabaratnam, M., Vroegop, P. G., & Gangadharan, S. K. (2001) · Seizure · doi:10.1053/seiz.2000.0492 · Cited by 91
Van der Molen, M. J. W., Van der Molen, M. W., Ridderinkhof, K. R., Hamel, B. C. J., Curfs, L. M. G., & Ramakers, G. J. A. (2012) · Clinical Neurophysiology · doi:10.1016/j.clinph.2011.08.023 · Cited by 88
Production and organization of neocortical interneurons
Sultan, K. T., Brown, K. N., & Shi, S.-H. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00221 · Cited by 83
Aberrant differentiation of glutamatergic cells in neocortex of mouse model for fragile X syndrome.
Tervonen, T. A., Louhivuori, V., Sun, X., Hokkanen, M.-E., Kratochwil, C. F., Zebryk, P., Castrén, E., & Castrén, M. L. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.10.010 · Cited by 82
Development of Inhibitory Timescales in Auditory Cortex
Oswald, A.-M. M., & Reyes, A. D. (2010) · Cerebral Cortex · doi:10.1093/cercor/bhq214 · Cited by 81
Developmental and behavioural disturbances in 13 boys with fragile X syndrome
Largo, R. H., & Schinzel, A. (1985) · European Journal of Pediatrics · doi:10.1007/bf00442299 · Cited by 80
Parvalbumin immunoreactivity in the auditory cortex of a mouse model of presbycusis.
Martin del Campo, H. N., Measor, K. R., & Razak, K. A. (2012) · Hearing Research · doi:10.1016/j.heares.2012.08.017 · Cited by 76
Self-citationImpaired Critical Period Plasticity in Primary Auditory Cortex of Fragile X Model Mice
Kim, H., Gibboni, R., Kirkhart, C., & Bao, S. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3246-12.2013 · Cited by 74
Anderson, L. A., Christianson, G. B., & Linden, J. F. (2009) · Brain Research · doi:10.1016/j.brainres.2008.11.037 · Cited by 71
Deficits in Tactile Learning in a Mouse Model of Fragile X Syndrome
Arnett, M. T., Herman, D. H., & McGee, A. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109116 · Cited by 70
Casting a net on dendritic spines: The extracellular matrix and its receptors
Dansie, L. E., & Ethell, I. M. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20963 · Cited by 68
Self-citationJeevakumar, V., & Kroener, S. (2014) · Cerebral Cortex · doi:10.1093/cercor/bhu293 · Cited by 59
Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of Mice
Brewton, D. H., Kokash, J., Jimenez, O., Pena, E. R., & Razak, K. A. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00270 · Cited by 54
Self-citationSchiff, M. L., & Reyes, A. D. (2012) · Journal of Neurophysiology · doi:10.1152/jn.00208.2011 · Cited by 48
Development and Behavior of Male Toddlers With Fragile X Syndrome
Roberts, J. E., Hatton, D. D., & Bailey, D. B. (2001) · Journal of Early Intervention · doi:10.1177/10538151010240030601 · Cited by 40
Cortical neurogenesis in fragile X syndrome
Castrén, M. L. (2016) · Frontiers in Bioscience · doi:10.2741/s455 · Cited by 24
Perineuronal nets increase inhibitory GABAergic currents during the critical period in rats.
Liu (2013) · PubMed · doi:10.3980/j.issn.2222-3959.2013.02.02 · Cited by 23
Dahle, A. J. (1980) · Ear and Hearing · doi:10.1097/00003446-198005000-00016 · Cited by 2
Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R
Br�ckner, G., Grosche, J., Schmidt, S., H�rtig, W., Margolis, R. U., Delpech, B., Seidenbecher, C. I., Czaniera, R., & Schachner, M. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20001225)428:4
Miller (1999) · doi:10.1002/(sici)1096-8628(19990402)83:4
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Contractor, A., Ethell, I. M., & Portera‐Cailliau, C. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00967-6 · Cited by 186
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Metadata
- Authors
- Wen, T. H., Afroz, S., Reinhard, S. M., Palacios, A. R., Tapia, K., Binder, D. K., Razak, K. A., & Ethell, I. M.
- Affiliations
- University of California, Riverside (US)
- Corresponding author
- Razak, Khaleel A
- Ethell, Iryna M
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-10-13
- Volume
- 28
- Issue
- 11
- Pages
- 3951-3964
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC6188540
- OpenAlex
- W2763626521
- Semantic Scholar
- 83b8ef7c7618272f1557fd06aa2421fbc73c141a
- Cited by
- 165
- References
- 84
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 23 · 2023: 15 · 2022: 18 · 2021: 27 · 2020: 24 · 2019: 17 · 2018: 8
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Cerebral Cortex (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (NIH) (1U54 HD082008-01)
- US Army Medical Research (W81XWH-15-1-0436)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- fragile X syndrome, Fmr1 knockout mice, MMP-9, perineuronal nets, parvalbumin interneurons, auditory cortex, sensory hypersensitivity, autism spectrum disorder, inhibitory interneurons, auditory habituation, therapeutic target
- MeSH terms
- Animals, Auditory Cortex, Disease Models, Animal, Fragile X Syndrome, Interneurons, Male, Nerve Net, Parvalbumins, Mice, Knockout, Matrix Metalloproteinase 9, Fragile X Messenger Ribonucleoprotein 1, GABAergic Neurons
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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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