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Aggrecan Directs Extracellular Matrix-Mediated Neuronal Plasticity
Open accessAbstract
In the adult brain, the extracellular matrix (ECM) influences recovery after injury, susceptibility to mental disorders, and is in general a strong regulator of neuronal plasticity. The proteoglycan aggrecan is a core component of the condensed ECM structures termed perineuronal nets (PNNs), and the specific role of PNNs on neural plasticity remains elusive. Here, we genetically targeted the Acan gene encoding for aggrecan using a novel animal model. This allowed for conditional and targeted loss of aggrecan in vivo, which ablated the PNN structure and caused a shift in the population of parvalbumin-expressing inhibitory interneurons toward a high plasticity state. Selective deletion of the Acan gene in the visual cortex of male adult mice reinstated juvenile ocular dominance plasticity, which was mechanistically identical to critical period plasticity. Brain-wide targeting improved object recognition memory. SIGNIFICANCE STATEMENT The study provides the first direct evidence of aggrecan as the main functional constituent and orchestrator of perineuronal nets (PNNs), and that loss of PNNs by aggrecan removal induces a permanent state of critical period-like plasticity. Loss of aggrecan ablates the PNN structure, resulting in invoked juvenile plasticity in the visual cortex and enhanced object recognition memory.
Checked 2026-10-06 · 12 references not checked yet
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TL;DR
Using a conditional Acan knockout mouse, this study shows that aggrecan is required for perineuronal net (PNN) assembly and that removing it in adult visual cortex reinstates juvenile-like ocular dominance plasticity and improves object recognition memory. It identifies aggrecan as a main functional constituent and orchestrator of PNNs.
Key findings
- Brain-wide conditional deletion of Acan (Acan-loxP +/+ CreNes) caused complete loss of WFA-labeled PNNs and prevented aggregation of other PNN components; heterozygous Acan-loxP +/-CreNes mice had anatomically normal PNNs but reduced WFA staining intensity (WFA ANOVA p=0.000244; Tukey heterozygous vs targeted p=0.0001934).
- Both heterozygous and homozygous Acan knockout mice showed a shift toward lower parvalbumin (PV) expression in cortical PV+ interneurons compared with WT and Acan-loxP +/+ controls (>150 PV+ cells per group; ANOVA p<2e-16), suggesting a high-plasticity network state.
- Local AAV9.Cre injection into adult V1 abolished aggrecan and WFA labeling by 8 weeks (WFA intensity lower in injected vs contralateral hemisphere, p=0.0006, paired t-test, n=6 mice). Four days of monocular deprivation produced a significant ocular dominance shift in AAV9.Cre-injected Acan-loxP +/+ mice (p=0.003, n=7), with increased ipsilateral responses (p=0.02) and reduced contralateral responses (p=0.009), while no effect was seen in non-injected Acan-loxP +/+ mice (p=0.21, n=4) or AAV9.Cre-injected Acan-loxP +/- mice (p=0.32, n=3).
- In spontaneous object recognition, Acan-loxP +/+ CreNes mice retained memory at 24 hours, whereas WT, Acan-loxP +/+, and Acan-loxP +/-CreNes groups showed significant decline from 3-hour to 24-hour delays (WT p=0.02547; homozygous Acan-loxP +/+ p=0.001154; heterozygous Acan-loxP +/-CreNes p=0.01658; Acan-loxP +/+ CreNes p=0.3768).
Methods
- A conditional Acan-loxP mouse was generated from EUCOMM tm1a embryonic stem cells, converted to the tm1c allele, and crossed with Nestin-CRE for brain-wide deletion; local adult deletion used AAV9.hSyn.HI.eGFP-Cre injection into primary visual cortex.
- Histology and biochemistry included WFA and aggrecan staining, immunohistochemistry for PNN components and PV, Western blotting, and qPCR; plasticity was assessed by optical imaging of intrinsic signals before and after 4-day monocular deprivation, and memory by spontaneous object recognition at 3-hour and 24-hour delays.
- Experiments used male mice: histology at 3–4 months (n=3 per group), ocular dominance testing at 5–7 months (n=4, 3, and 7 across groups), and object recognition at ~3 months (>7 per group). Statistical analysis used R or GraphPad Prism with Shapiro-Wilk/F tests, Welch’s or paired t-tests, and ANOVA with Tukey post hoc tests.
Limitations
- The paper does not include a dedicated limitations section; it states prior technical limitations such as off-target effects of chondroitinase ABC and embryonic lethality of Acan mutation, which motivated the new model.
- Evident from the text: all reported experiments used male mice only, ocular dominance groups were small (n=3–7), and memory was assessed only with spontaneous object recognition.
- Heterozygous Acan-loxP +/-CreNes mice showed reduced PNN intensity and altered PV expression but no detected behavioral alterations, indicating that some PNN/PV changes did not translate into the tested memory phenotype.
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30 Own result · 28 Not checked yet · 21 Own interpretation · 5 Own method
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In the paper
“Ablation of aggrecan was verified by immunohistochemistry and western blotting (Fig. 1c, d)”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“although the intensity of the WFA staining was reduced in the heterozygote (Fig. 2b-e).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The WFA histochemical signal specifically and quantitatively reflects the presence of PNNs.
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In the paper
“Targeting aggrecan in the brain of Acan-loxP +/+ CreNes mice was accompanied by complete loss of histochemical staining of PNNs in the cortex using the PNN marker Wisteria floribunda agglutinin (WFA) (Fig. 1b).”
- Also stated in: § Abstract · plain
“Loss of aggrecan ablates the PNN structure”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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- Also stated in: § Abstract · plain
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“and reduced Acan mRNA in the brain (Fig. 1e).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“Again, loss of aggrecan disrupted aggregation of the other PNN components (Fig. 3e)”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“Our data also show that populations of PV+ interneurons in both homozygous and heterozygous Acan-loxP +/+ -CreNes mice are shifted to a state where they express less PV (Fig. 2).”
- Also stated in: § REFERENCES: · hedged
“Categorization of individual cells based on mean PV intensity indicated a shift towards a low PV network configuration in the Acan-loxP +/-Cre and Acan-loxP +/+ Cre groups compared to controls.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
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In the paper
“Removal of aggrecan abolishes aggregation of PNNs, and essentially also incorporation of other ECM components into the structure (Fig 1 and 3).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
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“After 8 weeks all PNNs in the injected area in V1 were abolished.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > REFERENCES:
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“alterations in their behavior were not detected.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“Categorization of individual cells based on mean PV intensity indicated a shift towards a low PV network configuration in the Acan-loxP +/-Cre and Acan-loxP +/+ Cre groups compared to controls.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > REFERENCES:
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“Local injections of AAV9.Cre in adult Acan-loxP +/+ mice caused a complete loss of aggrecan and WFA labeling in V1 eight weeks after virus injection (Fig. 3b, c).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“Tracing of the connections between the lateral geniculate nucleus and V1 revealed normal retinotopic connectivity between V1 and lateral geniculate nucleus in the thalamus in the non-targeted Acan-loxP +/+ animal (Fig. 4a).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“Both Acan-loxP +/-Cre and Acan-loxP +/+ Cre groups displayed a significant reduction in average mean intensity per PV+ cell compared to WT and Acan-loxP +/+ controls.”
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“we observed changes in responsiveness to both contra -and ipsilateral inputs to V1 (Fig. 4), similar to how this shift occurs in CP aged animals.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
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“Following the three hours delay between sample and choice phases, all groups displayed a good ability to recognize the novel from familiar objects (discrimination ratio > 0.25).”
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“The combined expression of GFP and Cre by the virus revealed loss of PNNs surrounding infected neurons”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“We did not see the adult OD plasticity pattern, characterized by strengthening of ipsilateral input to V1.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“Selective deletion of the Acan gene in the visual cortex of male adult mice reinstated juvenile ocular dominance plasticity”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Abstract
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In the paper
“We show that PNN removal by aggrecan knock-out improves object recognition memory (Fig. 5), in line with previous work (Romberg et al., 2013).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Romberg et al., 2013
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“In both the heterozygous Acan-loxP +/-CreNes mice and homozygous Acan-loxP +/+ CreNes mice there was a shift towards lower PV expression by PV+ interneurons in the cortex compared to wild type and Acan-loxP +/+ controls (Fig 2f-h)”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“Brain-wide targeting improved object recognition memory.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Abstract
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“Local knock-out of Acan in V1 removed staining for aggrecan as well as Crtl-1, tenascin-R, versican and neurocan.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > REFERENCES:
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“Fluorescence intensity measurements of WFA staining were significantly lower in the AAV9.Cre treated area compared to the corresponding area in the contralateral untreated hemisphere, p=0.0006 (paired t-test, n=6 mice).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > REFERENCES:
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“Remarkably, the object recognition memory in the Acan-loxP +/+ CreNes group was still sustained at 24 hours after object exposure (Fig. 5c)”
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“A significant decrease in object recognition ability was detected in the WT, Acan-loxP +/+ and Acan-loxP +/-Cre groups following a 24 delay between sample and choice phases while Acan-loxP +/+ Cre did not.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“At 24 hours of the sample phase, the wild type, Acan-loxP +/+ and Acan-loxP +/-CreNes groups (Fig. 5c) showed little remaining memory.”
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“Strikingly, four days of MD were sufficient to produce a strong and significant shift in OD in adult AAV9.Cre injected Acan-loxP +/+ mice”
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“In AAV9.Cre injected Acan-loxP +/+ mice, MD caused a significant shift in activation towards the open eye (p=0.003,paired t-test, n=7 mice).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“In contrast, knock-out of the link protein Ctrl1 has been shown to give only a partial reduction of WFA-positive PNNs (Carulli et al., 2010).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
What the sources say
- Not checked yetcites Carulli et al., 2010
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“Aggrecan in PNN formation has only been studied in vitro (Giamanco et al., 2010;Kwok et al., 2010)”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > INTRODUCTION
What the sources say
- Not checked yetcites Giamanco et al., 2010
- Not checked yetcites Kwok et al., 2010
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“as mutation in the Acan gene results in embryonic lethality due to the lack of cartilage in the trachea and other critical structures (Rittenhouse et al., 1978).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > INTRODUCTION
What the sources say
- Not checked yetcites Rittenhouse et al., 1978
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“These perineuronal nets (PNNs) are enriched in chondroitin sulfate proteoglycans (CSPGs) and associated matrix molecules (Hartig et al., 1994;Deepa et al., 2006).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > INTRODUCTION
What the sources say
- Not checked yetcites Hartig et al., 1994
- Not checked yetcites Deepa et al., 2006
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In the paper
“The crucial dependence of aggrecan for PNN formation is in line with previous results from in vitro models demonstrating that aggrecan, link protein and hyaluronic acid are essential components of net formation and stability (Giamanco et al., 2010;Kwok et al., 2010).”
- Also stated in: § RESULTS · boosted
“Together, these targeting experiments demonstrate an essential role for aggrecan in PNN formation.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
What the sources say
- Not checked yetcites Giamanco et al., 2010
- Not checked yetcites Kwok et al., 2010
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- Also stated in: § RESULTS · boosted
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In the paper
“These results are very similar to those obtained after ChABC treatment and in Crtl1 knockouts, suggesting that the Acan knockout affects memory through effects on glycan chains in PNNs.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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- Rests on an assumption: ChABC treatment to degrade perineuronal nets shifted the network to a low-parvalbumin state, indicating that the glycans on CSPGs are a key component in controlling parvalbumin interneuron influence on network state.
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In the paper
“indicating that even partial attenuation of the Acan gene induces a low-PV state.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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“PNNs probably control synaptic plasticity and dynamics through several mechanisms.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
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In the paper
“which was mechanistically identical to critical period plasticity.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Abstract
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In the paper
“In the current study, the Acan-loxP mouse line has established a role for this CSPG in the control of plasticity in visual cortex and in memory.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
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“and may play a central role in regulating adult brain plasticity.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
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- Rests on an assumption: Aggrecan-containing perineuronal nets play an essential role in regulation of brain plasticity.
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“The study provides the first direct evidence of aggrecan as the main functional constituent and orchestrator of PNNs”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Abstract
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“The synapsin promoter restricted expression to neurons.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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- Based: passes — The paper gives a reason why it holds.
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
“demonstrating that expression of aggrecan by neurons is needed to form the PNN structure.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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.
- Rests on an assumption: The WFA histochemical signal specifically and quantitatively reflects the presence of PNNs.
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
“specific loss of PNNs increase adult brain plasticity.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > 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 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
“indicating plasticity mechanisms similar to juvenile animals (Fig. 4d).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“These effects differ from other manipulations to activate adult cortical plasticity such as Lynx1 deletion (Morishita et al., 2010), which arises as a result of potentiated responses to ipsilateral stimuli.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Morishita et al., 2010
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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In the paper
“Aggrecan is an efficient cross-linker interacting with hyaluronic acid and link protein by its N-terminal G1 domain and the extensively CS GAG modified central domain (Morawski et al., 2012).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Morawski et al., 2012
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 conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that Acan-loxP +/+ -CreNes mice are in a state of high network plasticity.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
hedged- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“previous work has shown that PNN removal reduces the activity of PV+ neurons (Balmer, 2016;Lensjo et al., 2017).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Balmer, 2016
- Not checked yetcites Lensjo et al., 2017
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 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
“its removal reopens juvenile plasticity in visual cortex”
- Also stated in: § DISCUSSION · plain
“Removal of aggrecan collapses the PNN structure and leads to a persistent state of juvenile-like plasticity.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > 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 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
“Aggrecan is the key component for assembling and sustaining the PNNs structure and function in the adult brain”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > 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.
In the paper
“our recent work which showed that brief MD in adult rats following enzymatic degradation of PNNs caused a similar effect on recorded single units in V1, in both hemispheres relative to the deprived eye (Lensjo et al., 2017).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Lensjo et al., 2017
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 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
“we established a conditional knock-out model for aggrecan and demonstrate that aggrecan is indeed required for the aggregation of PNNs”
- Also stated in: § DISCUSSION · boosted
“This work reveals that aggrecan is essential for PNN formation in vivo”
- Also stated in: § DISCUSSION · plain
“Removal of aggrecan abolishes aggregation of PNNs, and essentially also incorporation of other ECM components into the structure (Fig 1 and 3).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > 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.
- Also stated in: § DISCUSSION · boosted
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, this suggest that the PNN is a determinant factor in closure of the CPs in juvenile development, through its effect on PV+ neurons and action as a structural barrier.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
hedgeddirect- 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.
- Rests on an assumption: Condensation of perineuronal nets in sensory cortices correlates with closure of periods of heightened neuronal plasticity in sensory systems.
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 aggrecan is essential for sustaining PNNs in the visual cortex.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
hedgeddirect- 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.
- Rests on an assumption: The WFA histochemical signal specifically and quantitatively reflects the presence of PNNs.
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
“indicating a stronger recognition memory in mice lacking aggrecan.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
hedgeddirect- 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 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
“loss of PNNs by aggrecan removal induces a permanent state of critical period-like plasticity.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Abstract
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.
- Rests on an assumption: The mouse visual cortex is a valid model for studying critical period plasticity.
In the paper
“and affects memory processing.”
- Also stated in: § DISCUSSION · plain
“We show that PNN removal by aggrecan knock-out improves object recognition memory (Fig. 5), in line with previous work (Romberg et al., 2013).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Romberg et al., 2013
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
In the paper
“This has been shown to be an important factor in regulation of CP plasticity (Hensch, 2004)”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Hensch, 2004
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. 15
- Probably not a substantial claim. 14
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 contrast, the non-targeted Acan-loxP +/+ mice with two intact alleles expressing Acan, and the targeted heterozygous Acan-loxP +/-CreNes mice having one intact allele, both had anatomically normal PNNs (Fig. 1b, f)”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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.
- Rests on an assumption: The WFA histochemical signal specifically and quantitatively reflects the presence of PNNs.
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 loss of aggrecan prevented aggregation of other PNN component ECM molecules into PNNs, effectively abolishing PNNs in the adult cortex (Fig. 1f, representative example from > 50 images per PNN component.Fig. 2a, overview of sampling).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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.
- Rests on an assumption: The WFA histochemical signal specifically and quantitatively reflects the presence of PNNs.
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 heterozygous Acan-loxP +/-CreNes have reduced PNNs intensity and altered PV expression”
- Also stated in: § REFERENCES: · plain
“Both Acan-loxP +/-Cre and Acan-loxP +/+ Cre groups displayed a significant reduction in average mean intensity per PV+ cell compared to WT and Acan-loxP +/+ controls.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
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.
- Also stated in: § REFERENCES: · 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
“Instead, the shift in OD was driven both by a potentiation of ipsilateral responses and a reduction in contralateral responses”
- Also stated in: § REFERENCES: · plain
“The MD in AAV9.Cre injected Acan-loxP +/+ caused both increased responses to ipsilateral stimulation (p=0.02,paired t-test, n=7 mice) and reduced responses to contralateral stimulation (p=0.009,paired-test, n=7 mice)”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
plaindirectn = 7 ·- 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.
- Also stated in: § REFERENCES: · 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 no effect was observed in AAV9.Cre injected Acan-loxP +/-mice or non-injected Acan-loxP +/+ mice (Fig. 4c).”
- Also stated in: § REFERENCES: · plain
“Four days of MD did not affect ocular dominance in non-injected Acan-loxP +/+ mice (p=0.21,paired t-test, n=4 mice) or in heterozygous AAV9.Cre injected Acan-loxP +/-mice (p=0.32,paired t-test, n=3 mice).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
plainn = 4- 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.
- Also stated in: § REFERENCES: · plain
In the paper
“Closure of the CPs and concomitant loss of juvenile plasticity coincide with maturation of inhibitory circuits (Hensch, 2004) and condensation of extracellular matrix around subtypes of neurons.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > INTRODUCTION
What the sources say
- Not checked yetcites Hensch, 2004
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.
None of the sources cited for this claim have been checked yet.
In the paper
“However, the identity of the CSPG responsible for these effects has not been determined.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > INTRODUCTION
What the sources say
- Not checked yetcites Pizzorusso et al., 2002
- Not checked yetcites Carulli et al., 2010
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.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Remarkably, enzymatically degrading the CS glycosaminoglycan (GAG) component (Pizzorusso et al., 2002) or ablating the cross-linking cartilage link protein 1 (Crtl1) (Carulli et al., 2010) restores juvenile plasticity in the adult animal and affects memory and learning, as revealed by behavioral tasks such as fear memory extinction (Gogolla et al., 2009) and spontaneous object recognition (Romberg”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > INTRODUCTION
What the sources say
- Not checked yetcites Pizzorusso et al., 2002
- Not checked yetcites Carulli et al., 2010
- Not checked yetcites Gogolla et al., 2009
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.
In the paper
“The proteoglycan aggrecan is a core component of the condensed ECM structures termed perineuronal nets (PNNs)”
- Also stated in: § INTRODUCTION · plain
“Here we investigate the role of the CSPG aggrecan, a major constituent of PNNs, encoded by Acan (Matthews et al., 2002).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Abstract
What the sources say
- Not checked yetcites Matthews et al., 2002
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.
- Also stated in: § INTRODUCTION · plain
None of the sources cited for this claim have been checked yet.
In the paper
“In the adult brain, the extracellular matrix (ECM) influences recovery after injury, susceptibility to mental disorders, and is in general a strong regulator of neuronal plasticity.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Abstract
What the sources say
- Not checked yetcites Pizzorusso et al., 2002
- Not checked yetcites Carulli et al., 2010
- Not checked yetcites Gogolla et al., 2009
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.
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 increased plasticity after PNN removal could also be a direct consequence of neuronal activity changes in PV + cells.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
hedgedconditional- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“the specific role of PNNs on neural plasticity remains elusive.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Abstract
What the sources say
- Not checked yetcites Pizzorusso et al., 2002
- Not checked yetcites Carulli et al., 2010
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.
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
“The maze and all objects were wiped down with 70% EtOH in between each testing session in order to avoid any olfactory bias that could have been introduced during the previous testing session.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Brain-wide and developmental Cre-lox recombination by Nestin-CRE
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.
In the paper
“Recently, parvalbumin (PV) expression on GABAergic interneurons has been shown to be influenced by PNNs in the hippocampus (Yamada et al., 2015)”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
What the sources say
- Not checked yetcites Yamada et al., 2015
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.
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 three globular domains; G1, G2 and G3 interact with several matrix molecules aiding cross-linking, which could explain the failure of other components to aggregate in its absence.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > 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.
- Rests on an assumption: Perineuronal net structure is based on tight cross-linking of matrix proteins, chondroitin sulfate and hyaluronic acid polysaccharides forming a condensed compact matrix, and on negatively charged sulfation patterns allowing specific interactions with positively charged domains in PNN interacting proteins.
In the paper
“Animals were tested after three and 24 hour delays, at which times ChABC-treated and Crtl1 knockout animals show enhanced memory retention (Romberg et al., 2013).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
What the sources say
- Not checked yetcites Romberg et al., 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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The timeframe of this shift is faster than what has been observed in CP aged mice (Sato and Stryker, 2008), but is in line with previous work on adult mice with induced plasticity (Fu et al., 2015).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Sato and Stryker, 2008
- Not checked yetcites Fu et al., 2015
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Several interventions affecting PNNs have effects on learning and memory (Gogolla et al., 2009;Carulli et al., 2010;Romberg et al., 2013).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
What the sources say
- Not checked yetcites Gogolla et al., 2009
- Not checked yetcites Carulli et al., 2010
- Not checked yetcites Romberg et al., 2013
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.
In the paper
“Others have suggested that the level of PV in PV+ interneurons determine if the network is in a state of high or low plasticity (Donato et al., 2013)”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Donato et al., 2013
hedgeddirect- Asserted: fails — The authors may not 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 authors may not put it forward as true. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The presentation of the object pairs and their appearance in either the left or right sample arm were counterbalanced so that a particular object in a set or a particular side might be novel for one animal and not for another to avoid unforeseen bias.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Brain-wide and developmental Cre-lox recombination by Nestin-CRE
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.
In the paper
“and the differentiation state and activity of PV+ interneurons relate to learning and memory formation (Donato et al., 2013).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
What the sources say
- Not checked yetcites Donato et al., 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.
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
“To reduce variance in antibody binding all groups used for quantification were histologically stained in batches using the same conditions and antibody solutions.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Brain-wide and developmental Cre-lox recombination by Nestin-CRE
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.
In the paper
“Indeed, the ratio of 4-and 6-sulfated CS influences neuronal plasticity (Miyata et al., 2012).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Miyata et al., 2012
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.
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 tracer injections were intentionally targeted to a more medial part of V1 to prevent leakage into the neighboring V2L region.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Brain-wide and developmental Cre-lox recombination by Nestin-CRE
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.
In the paper
“A shift in the distribution of WFA histochemical labeling intensity has been suggested to correlate with the degree of neuronal plasticity in learning and memory (Balmer et al., 2009).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
What the sources say
- Not checked yetcites Balmer et al., 2009
hedgedcorrelational- 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 data suggest that aggrecan plays a key role for the PNN structure, possibly through the large number of glycan chains that it carries, but clearly by affecting formation.”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > 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.
- Rests on an assumption: Perineuronal net structure is based on tight cross-linking of matrix proteins, chondroitin sulfate and hyaluronic acid polysaccharides forming a condensed compact matrix, and on negatively charged sulfation patterns allowing specific interactions with positively charged domains in PNN interacting proteins.
None of the sources cited for this claim have been checked yet.
In the paper
“Longer lasting sensory deprivation has been shown to induce some OD plasticity also in adult mice, but the mechanism differs from juvenile plasticity (Sawtell et al., 2003;Ranson et al., 2012).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
What the sources say
- Not checked yetcites Sawtell et al., 2003
- Not checked yetcites Ranson et al., 2012
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Recently, aggrecan and PNNs have been implied in various psychiatric disorders (Pantazopoulos et al., 2015), and in the progression of neurodegenerative diseases (Suttkus et al., 2016).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > DISCUSSION
What the sources say
- Not checked yetcites Pantazopoulos et al., 2015
- Not checked yetcites Suttkus et al., 2016
hedgedcorrelational- 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.
The paper relies on this without support.
The WFA histochemical signal specifically and quantitatively reflects the presence of PNNs.
“using the PNN marker Wisteria floribunda agglutinin (WFA)”
“PNNs detected by WFA were absent in the brain.”
The paper relies on this without support.
The mouse visual cortex is a valid model for studying critical period plasticity.
“Selective deletion of the Acan gene in the visual cortex of male adult mice reinstated juvenile ocular dominance plasticity”
The paper relies on this without support.
The role of aggrecan, the backbone of perineuronal nets, in plasticity regulation remains to be investigated, and a full picture of plasticity regulation is lacking.
“Although several PNN CSPGs have been linked to plasticity regulation, the role of aggrecan, the backbone of PNN remains to be investigated, and a full picture of plasticity regulation is lacking.”
The paper relies on this without support.
Aggrecan-containing perineuronal nets play an essential role in regulation of brain plasticity.
“It has been suggested that aggrecan-containing PNNs play an essential role in regulation of brain plasticity.”
The paper relies on this without support.
Condensation of perineuronal nets in sensory cortices correlates with closure of periods of heightened neuronal plasticity in sensory systems.
“Condensation of PNNs in sensory cortices correlates with closure of periods of heightened neuronal plasticity in sensory systems.”
The paper relies on this without support.
Monocular deprivation in adults normally affects only responses to ipsilateral eye stimulation.
“While monocular deprivation in adults normally effects only responses to ipsilateral eye stimulation”
The paper relies on this without support.
Decreased parvalbumin expression and synapses are associated with hippocampal learning, while fear conditioning leads to a high-parvalbumin state.
“Decreased PV expression and synapses are associated with hippocampal learning, while fear conditioning leads to a high-PV state.”
The paper relies on this without support.
Parvalbumin-positive neuron-controlled shifts in network state are an integrated mechanism of learning and memory acquisition.
“PV+ neuron-controlled shifts in network state are suggested as an integrated mechanism of learning and memory acquisition.”
The paper relies on this without support.
ChABC treatment to degrade perineuronal nets shifted the network to a low-parvalbumin state, indicating that the glycans on CSPGs are a key component in controlling parvalbumin interneuron influence on network state.
“ChABC treatment to degrade PNNs shifted the network to a low-PV state, indicating that the glycans on CSPGs are a key component in controlling PV interneuron influence on network state.”
The paper relies on this without support.
Mounting evidence from other brain structures supports a broader role for perineuronal nets where they affect behavior, memory and learning processes.
“Mounting evidence from other brain structures supports a broader role for PNNs where they affect behavior, memory and learning processes.”
The paper relies on this without support.
Perineuronal net structure is based on tight cross-linking of matrix proteins, chondroitin sulfate and hyaluronic acid polysaccharides forming a condensed compact matrix, and on negatively charged sulfation patterns allowing specific interactions with positively charged domains in PNN interacting proteins.
“These mechanisms are based on the distinctive PNN structure; the tight cross-linking structures of matrix proteins, CS and hyaluronic acid polysaccharides forming a condensed compact matrix surrounding the cell soma and proximal dendrites, and the ability of the negatively charged sulfation patterns of the CS to allow specific interactions with positively charged domains in PNN interacting”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In line with this, digestion of CSPGs in the primary visual cortex in rats or deletion of aggrecan in mice decreases inhibitory activity, causing the network to revert to an immature juvenile state and an increased level of activity-dependent plasticity [47, 69].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [69]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Similarly, disaggregation of PNNs by genetic deletion of aggrecan shifts the population of PV inhibitory interneurons toward a juvenile-like plasticity state, accompanied by increased performance in the SOR memory task [69].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [69]
In the citing paper
“enhanced plasticity and learning is observed following experimental PNN ablation [23, 24]”
From Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain (2020) · cites this paper as [24]
In the citing paper
“Finally, disease-related effects on PNNs were validated at 12mo by staining for aggrecan, a core PNN CSPG [24], which confirmed the morphological abnormalities as well as the loss of 5xFAD subiculum and cortical PNNs at this timepoint (p<0.001, p<0.05; Fig. S2D-F).”
From Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain (2020) · cites this paper as [24]
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
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
“In this paradigm, depicted in figure 5a, animals (> 7 per group) identify novel from familiar objects (choice phase) following a delay from familiar object presentation (sample phase).”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > EXPERIMENTAL DESIGN AND STATISTICAL ANALYSIS
“There were 7, 9 (which of one was singly housed), 10 and 7 male animals of ~3 months of age originating same line of breeding in each of the 4 experimental groups; WT, Acan-loxP (+/+) , Acan-loxP (+/-) Cre, and Acan-loxP (+/+) Cre.”
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
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > RESULTS
“AAV9.hSyn.HI.eGFP.WPRE.SV40 (AAV9.Cre) carrying Cre recombinase”
§ Aggrecan directs extracellular matrix mediated neuronal plasticity > Brain-wide and developmental Cre-lox recombination by Nestin-CRE
“AAV9.hSyn.HI.eGFP-Cre.WPRE.SV40 (Catalog number AV-9-PV1848)”
Citations
Cites
Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
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A conditional knockout resource for the genome-wide study of mouse gene function
Skarnes, W. C., Rosen, B., West, A. P., Koutsourakis, M., Bushell, W., Iyer, V., Mujica, A. O., Thomas, M., Harrow, J., Cox, T., et al. (2011) · Nature · doi:10.1038/nature10163 · Cited by 1,708
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
Self-citationHensch, T. K. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144327 · Cited by 1,300
EBImage—an R package for image processing with applications to cellular phenotypes
Pau, G., Fuchs, F., Sklyar, O., Boutros, M., & Huber, W. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq046 · Cited by 799
Perineuronal Nets Protect Fear Memories from Erasure
Gogolla, N., Caroni, P., Lüthi, A., & Herry, C. (2009) · Science · doi:10.1126/science.1174146 · Cited by 760
Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning
Donato, F., Rompani, S. B., & Caroni, P. (2013) · Nature · doi:10.1038/nature12866 · Cited by 703
New Paradigm for Optical Imaging
Kalatsky, V. A., & Stryker, M. P. (2003) · Neuron · doi:10.1016/s0896-6273(03)00286-1 · Cited by 571
Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity
Frischknecht, R., Heine, M., Perrais, D., Seidenbecher, C. I., Choquet, D., & Gundelfinger, E. D. (2009) · Nature Neuroscience · doi:10.1038/nn.2338 · Cited by 554
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
Self-citation
Cited by
Sorted by citations
Perineuronal nets stabilize the grid cell network
Christensen, A. C., Lensjø, K. K., Lepperød, M. E., Dragly, S.-A., Sutterud, H., Blackstad, J. S., Fyhn, M., & Hafting, T. (2021) · Nature Communications · doi:10.1038/s41467-020-20241-w · Cited by 1,865
Self-citationMicroglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity
Nguyen, P. T., Dorman, L. C., Pan, S., Vainchtein, I. D., Han, R. T., Nakao-Inoue, H., Taloma, S. E., Barron, J. J., Molofsky, A. B., Kheirbek, M. A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.050 · Cited by 615
The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function
Fawcett, J. W., Oohashi, T., & Pizzorusso, T. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0196-3 · Cited by 589
Self-citationMicroglia facilitate loss of perineuronal nets in the Alzheimer's disease brain
Crapser, J. D., Spangenberg, E. E., Barahona, R. A., Arreola, M. A., Hohsfield, L. A., & Green, K. N. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102919 · Cited by 280
Perineuronal Nets: Plasticity, Protection, and Therapeutic Potential
Reichelt, A. C., Hare, D. J., Bussey, T. J., & Saksida, L. M. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.04.003 · Cited by 219
Metadata
- Authors
- Rowlands, D., Lensjø, K. K., Dinh, T., Yang, S., Andrews, M. R., Hafting, T., Fyhn, M., Fawcett, J. W., & Dick, G.
- Affiliations
- University of Oslo (NO)
- University of Cambridge (GB)
- University of Southampton (GB)
- Czech Academy of Sciences (CZ)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2018-10-03
- Volume
- 38
- Issue
- 47
- Pages
- 10102-10113
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6596198
- OpenAlex
- W2894865807
- Semantic Scholar
- 9d76c8f2d73c04f3367a993907c15081487d05ea
- Cited by
- 204
- References
- 37
- Citations by year
- 2026: 20 · 2025: 40 · 2024: 30 · 2023: 23 · 2022: 33 · 2021: 17 · 2020: 26 · 2019: 14 · 2018: 1
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- Christopher and Dana Reeve Foundation
- Universitetet i Oslo
- Norges Forskningsråd (231248)
- Medical Research Council (MR/R004544/1, MR/R004463/1)
- Biotechnology and Biological Sciences Research Council (BB/N008189/1)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- aggrecan, perineuronal nets, extracellular matrix, neuroplasticity, parvalbumin interneurons, ocular dominance plasticity, critical period plasticity, visual cortex, object recognition memory, conditional gene deletion, proteoglycans
- MeSH terms
- Animals, Cell Line, Extracellular Matrix, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Neuronal Plasticity, Photic Stimulation, Visual Cortex, Mice, Knockout, Mice, Aggrecans
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.
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