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Cited by 101Neuroscience and Neuropharmacology ResearchProtease and Inhibitor MechanismsNeurogenesis and neuroplasticity mechanisms

Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin

Open access
Rossier, J, Bernard, A, Cabungcal, J-H, Perrenoud, Q, Savoye, A, Gallopin, T, Hawrylycz, M, Cuénod, M +3 more·2015·Molecular Psychiatry
DOI 10.1038/mp.2014.162PMC PMC4356748
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Abstract

The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only four were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β-peptides. The pattern of expression of metalloproteases (MPs) was analyzed by single-cell reverse transcriptase multiplex PCR after patch clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas. Clustering of these genes by K-means algorithm displays five distinct clusters. Among these five clusters, two fast-spiking interneuron clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not.

AI snapshot

Written from the paper’s full text.

TL;DR

Mining the Allen Mouse Brain Atlas and single-cell RT-mPCR after patch clamp identified a subpopulation of fast-spiking parvalbumin interneurons in mouse somatosensory cortex that co-expresses Adamts8, Adamts15 and Mme/Neprilysin and is enwrapped by perineuronal nets. A separate PV-Sst subpopulation lacks these metallopeptidases and is not surrounded by perineuronal nets.

Key findings

  • Among 480 protease/peptidase genes, only four were enriched in cortical interneurons: Reln, Adamts8, Adamts15 and Mme (Neprilysin).
  • scRT-mPCR after patch clamp of 218 neurons, followed by K-means clustering, split fast-spiking Pvalb interneurons into two subclusters: PV-Sst (Pvalb + Sst) and PV-MP (Pvalb + Adamts8, Adamts15, Mme). PV-MP comprised 39 cells and PV-Sst 26 cells.
  • Both PV subclusters had maximal discharge frequency >130 Hz, but PV-MP cells discharged at higher maximal frequency and were less excitable, with lower mean input resistance and higher rheobase values than PV-Sst cells.
  • Using Wisteria floribunda agglutinin (WFA) as a perineuronal net marker, PV-MP interneurons were surrounded by PNN, whereas Sst-expressing and PV-Sst interneurons were not. dFISH and immunostaining confirmed coexpression of Pvalb with Adamts8, Mme and Mybpc1, and lack of colocalization with Sst.

Methods

  • Juvenile C57BL/6 mice (P14–P17) were used for somatosensory cortex slices; whole-cell patch-clamp recordings were performed in current-clamp mode, and cell contents were aspirated for single-cell reverse transcriptase multiplex PCR (scRT-mPCR).
  • scRT-mPCR detected 27 genes (26 interneuron genes plus Slc17a7/VGluT1) using nested primer pairs and agarose gel detection; clustering used Ward’s hierarchical and K-means on binarized expression values, with K-means k=6 selected by clustergram stability analysis.
  • Validation used double-fluorescent in situ hybridization and immunofluorescence/confocal imaging with WFA and antibodies against parvalbumin, somatostatin, ADAMTS8, Neprilysin and Mybpc1 in adult mouse cortex.

Limitations

  • Stated: generalization of the PV-MP/PV-Sst and PNN association to other cortical areas remains to be done; chandelier interneurons were not identified in the slice preparations; the role of Mybpc1 in the PV-MP cluster is still unknown.
  • Evident: the study reports expression patterns and anatomical associations rather than causal manipulation, so whether these secreted metallopeptidases directly reshape the PNN or affect plasticity/memory is not tested.
  • Evident: simultaneous scRT-mPCR detection of all three metallopeptidases was rare (4/39 PV-MP cells), with two of the three detected in 10/39 PV-MP cells, so co-expression conclusions rely on combined scRT-mPCR, dFISH and immunostaining evidence.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/mp.2014.162

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 37 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    Only four protease/peptidase genes were found enriched in cortical interneurons: Reln, Adamts8, Adamts15 and Mme.

    “Among the 480 genes coding for protease/peptidases, only four were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β-peptides.”
    • Also stated in: § Introduction · plain
      “In the six layers of the somatosensory cortex, 1043 genes were expressed in various specific neuronal populations, 22 of these genes belonged to the class of protease/peptidases and only 4 proteases/peptidases were expressed preferentially in interneurons (Table 1 and see Supplementary Table S1 in Sorensen et al.8).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sorensen et al.8 Sorensen SA, Bernard A, Menon V, Royall JJ, Glattfelder KJ, Desta T et al. Correlated gene expression and target specificity demonstrate excitatory projection neuron diversity. Cereb Cortex 2013 doi: 10.1093/cercor/bht243 (e-pub ahead of print). source

      Not checked in the free run.

  • Findingown data

    Neurons from both PV subclusters display a maximal discharge frequency >130 Hz, a feature typical of FS-PV cells.

    “Neurons from both PV subclusters display a maximal discharge frequency >130 Hz (Table 2), a feature typical of FS-PV cells.9”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Ascoli GA, Alonso-Nanclares L, Anderson SA, Barrionuevo G, Benavides-Piccione R, Burkhalter A et al. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat Rev Neurosci 2008; 9: 557–568. source

      Not checked in the free run.

  • Findingown data

    dFISH analysis confirms that mRNA for Mybpc1 and for the three MPs are coexpressed with Pvalb in all layers of the somatosensory cortex.

    “dFISH analysis of Mybpc1, Mme, Adamts8 and Adamts15 with Pvalb was performed and confirms that mRNA for Mybpc1 and for the three MPs are coexpressed with Pvalb in all layers of the somatosensory cortex.”
    Quote in the paperSubstantial claim
  • Findingown data

    Slc17a7 (VGluT1) was detected in almost 20% of the interneurons.

    “In this study, Slc17a7 (VGluT1), the canonical marker for excitatory neurons, was detected in almost 20% of the interneurons.”
    Quote in the paperNot a substantial claim
  • Findingown data

    K-means cluster stability analysis showed that a K-means value of 6 provided the best separation between clusters.

    “As shown, in Figure 1b, the cluster stability analysis showed that a K-means value of 6 (k=6) provided the best separation between clusters.”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • The quote only partly states this claim. 2
  • Classified as probably not a substantial claim. 22

  • May combine two claims.

    Findingown data

    PV-MP interneurons were found surrounded by PNN, whereas PV-Sst interneurons were not.

    “By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not.”
    • Also stated in: § Discussion · plain
      “By using WFA, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas interneurons expressing Sst and PV-Sst were not.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Wisteria floribunda agglutinin (WFA) specifically labels the perineuronal net (PNN).

  • May combine two claims.

    Findingown data

    PV-MP neurons discharge at higher frequency and are less excitable than the PV-Sst cluster.

    “These two FS-PV clusters differed also by their electrophysiological properties; the PV-MP neurons discharge at higher frequency and are less excitable than the PV-Sst cluster.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Adding metallopeptidase genes led to rearrangement of the FS-PV cluster into two subclusters, one expressing Sst (PV-Sst) and another expressing the three metallopeptidases (PV-MP) but not Sst.

    “Adding metallopeptidase genes lead to rearrangement of the FS-PV cluster in two subclusters, one expressing Sst (PV-Sst) and another one expressing these three metallopeptidases (PV-MPs), but not Sst.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    K-means clustering of the 27 genes displays five distinct clusters.

    “Clustering of these genes by K-means algorithm displays five distinct clusters.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Ward's hierarchical clustering identified five groups of neurons and discriminated excitatory neurons expressing Slc17a7 from inhibitory neurons expressing Gad1 and Gad2.

    “This algorithm identified five groups of neurons (Figure 1a) in agreement with previous findings10, 11 and discriminated excitatory neurons expressing Slc17a7 from inhibitory neurons expressing Gad1 and Gad2.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Karagiannis A, Gallopin T, Dávid C, Battaglia D, Geoffroy H, Rossier J et al. Classification of NPY-expressing neocortical interneurons. J Neurosci 2009; 29: 3642–3659. source

      Not checked in the free run.

    • cites [11] Perrenoud Q, Rossier J, Geoffroy H, Vitalis T, Gallopin T. . Diversity of GABAergic interneurons in layer VIa and VIb of mouse barrel cortex. Cereb Cortex 2013; 23: 423–441. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Among the five clusters, two fast-spiking interneuron clusters expressing Pvalb were identified: PV-Sst co-expressing Pvalb with Sst, and PV-MP co-expressing Pvalb with Adamts8, Adamts15 and Mme.

    “Among these five clusters, two fast-spiking interneuron clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The PV-MP cluster expresses the three peptidases and also Mybpc1.

    “This latter cluster expresses the three peptidases and also Mybpc1 whose role in this cluster is still unknown.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    K-means with k=6 dissociates the PV cluster into two subclusters, PV-Sst and PV-MP.

    “Figure 1a indicates that the K-means algorithm with a k of 6, now dissociates the PV cluster in two subclusters.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The KS cluster was subclustered into KS-VIP, expressing Vip with no Nxph1, and KS-NG, not expressing Vip but expressing Nxph1 at 17/35.

    “Similarly with the Ward's clustering, the KS cluster (yellow in Figure 1a) was subclustered in two subclasses, one (KS-VIP in green) expressing Vip with no expression of Nxph1, and another one, KS-NG (orange in Figure 1a) that does not express Vip but expresses Nxph1 at a relatively high occurrence (17/35).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Sst is not colocalized with Mybpc1 nor with WFA.

    “Figure 3e indicates that Sst (red) is not colocalized with Mybpc1 (green) nor with WFA.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Wisteria floribunda agglutinin (WFA) specifically labels the perineuronal net (PNN).

  • May combine two claims.

    Findingown data

    The Sst cluster expresses Sst (39/40), Calb1 (23/40) and Npy (34/40).

    “Sst cluster expresses Sst (39/40), Calb1 (23/40) and Npy (34/40).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Akr1c18, Mybpc1, Mme, Adamts8 and Adamts15 are expressed in the PV-MP cluster and seldom or not expressed in the PV-Sst cluster nor in the other clusters of inhibitory or excitatory neurons.

    “These two PV clusters are also different in the expression of five genes: Akr1c18, Mybpc1, Mme, Adamts8 and Adamts15 are expressed in PV-MP cluster and seldom expressed or neither in PV-Sst cluster nor in the other clusters of inhibitory or excitatory neurons.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Simultaneous detection by RT-PCR of Adamts8, Adamts15 and Mme was found in 4 of the 39 PV-MP cells; simultaneous detection of two of the three peptidases was found in 10 of 39.

    “Analysis of Figure 1 and Supplementary Table 2 indicates that simultaneous detection by RT-PCR of the three genes Adamts8, Adamts15 and Mme was found in 4 cells over the 39 cells of the cluster PV-MP; simultaneous detection of two genes among the three peptidases was found in 10 cells over 39.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The KS-NG cluster expressed Reln (28/35) and Pnoc (30/35).

    “The KS-NG cluster expressed glycoprotein serine protease reelin Reln (28/35) and the precursor of the anti-analgesic peptide, pronociceptin Pnoc (30/35).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The KS-NG subcluster contains 40% of LS neurons; the LS firing pattern is the electrophysiological signature of NG cells and was never observed in cells from other clusters.

    “This latter subcluster contains 40% of LS neurons characterized by a delay to generate action potentials (Supplementary Table S2). LS firing pattern is the electrophysiological signature of NG cells9 and was never observed in cells from other clusters.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Ascoli GA, Alonso-Nanclares L, Anderson SA, Barrionuevo G, Benavides-Piccione R, Burkhalter A et al. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat Rev Neurosci 2008; 9: 557–568. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    dFISH found colocalization for Pvalb with Adamts8, Mme and Mybpc1, and these three genes were never colocalized with Sst.

    “Colocalization was found for Pvalb and Adamts8 (red), Mme (green) and Mybpc1 (green) on the other hand these three genes (all three in green) were never colocalized with Sst (red).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Two classes of PV basket interneurons were identified in the somatosensory cortex of the adult mouse: PV interneurons expressing MP were surrounded by PNN and PV expressing Sst were not enwrapped by PNN.

    “The general conclusions of the ISH and immunocytological studies are that two classes of PV basket interneurons were identified in the somatosensory cortex of the adult mouse: PV interneurons expressing MP were surrounded by PNN and PV expressing Sst were not enwrapped by PNN.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Wisteria floribunda agglutinin (WFA) specifically labels the perineuronal net (PNN).

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

    Findingcitation

    In this work as well as in previous works, chandelier interneurons were not identified on the slice preparations.

    “In this work as well as in previous works10, 11 chandelier interneurons22 were not identified on the slice preparations.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [10] Karagiannis A, Gallopin T, Dávid C, Battaglia D, Geoffroy H, Rossier J et al. Classification of NPY-expressing neocortical interneurons. J Neurosci 2009; 29: 3642–3659. source

      Not checked in the free run.

    • cites [11] Perrenoud Q, Rossier J, Geoffroy H, Vitalis T, Gallopin T. . Diversity of GABAergic interneurons in layer VIa and VIb of mouse barrel cortex. Cereb Cortex 2013; 23: 423–441. source

      Not checked in the free run.

    • cites [22] Taniguchi H, Lu J, Huang ZJ . The spatial and temporal origin of chandelier cells in mouse neocortex. Science 2013; 339: 70–74. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The 39 PV-MP cells discharge at a higher maximal frequency than the 26 PV-Sst cells but are on average less excitable due to their lower mean input resistance and higher rheobase values.

    “When looking at their electrophysiological properties, these two subclasses of FS-PV displayed different characteristics: the 39 PV-MP cells discharge at a higher maximal frequency than the 26 PV-Sst cells but are on average, less excitable due to their lower mean input resistance and higher rheobase values (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Antibodies against ADAMTS8, Mme (Neprilysin) and Mybpc1 indicate that these markers are colocalized with PV and also with WFA.

    “In Figures 3b–d, antibodies against ADAMTS8, Mme (Neprilysin) and Mybpc1 indicate that these markers are colocalized with PV and also with WFA.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Wisteria floribunda agglutinin (WFA) specifically labels the perineuronal net (PNN).

  • May combine two claims.

    Findingown data

    Both VIP and NG clusters were enriched for Kit and Sema3c, which were barely expressed in other clusters; Kit and Sema3c define a single cluster named KS.

    “Both VIP and NG clusters were enriched for the two genes Kit and Sema3c. These genes were barely expressed in other clusters. Kit and Sema3c define a single cluster of cells named hereunder KS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Npy was detected in 31 of the 35 KS-NG cells but was also detected at high occurrence in Sst, PV-MP and PV-Sst clusters, confirming that Npy is not a specific marker for NG cells.

    “Npy was detected in 31 of the 35 cells of that cluster but was also detected at high occurrence in Sst, PV-MP and PV-Sst clusters, confirming that Npy is not a specific marker for NG cells.11”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Perrenoud Q, Rossier J, Geoffroy H, Vitalis T, Gallopin T. . Diversity of GABAergic interneurons in layer VIa and VIb of mouse barrel cortex. Cereb Cortex 2013; 23: 423–441. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    PV-stained cells are frequently, but not always, associated with WFA; Sst is not associated with WFA.

    “In the Supplementary Figure S1, panel A shows that PV-stained cells are frequently, but not always, associated with WFA, on the other hand panel B shows that Sst is not associated with WFA.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Wisteria floribunda agglutinin (WFA) specifically labels the perineuronal net (PNN).

  • May combine two claims.

    Findingown data

    The KS-VIP cluster expressed Vip (14/17), calretinin (Calb2) (9/17) and Htr3a (8/17); Vip was not expressed in the other clusters.

    “The KS-VIP cluster expressed with high occurrence Vip (14/17), calretinin (Calb2) (9/17) and ionotropic serotonin receptor subunit Htr3a (8/17). Vip was not expressed in the other clusters.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Single-cell reverse transcriptase multiplex PCR after patch clamp and unsupervised clustering of canonical interneuronal markers defined four classes of GABAergic interneurons: VIP, NG, Sst and FS-PV.

    “By using unsupervised clustering expression profiling of canonical interneuronal markers, four classes of GABAergic interneurons were defined: vasoactive intestinal peptide (VIP), neurogliaform (NG), somatostatin (Sst) and fast-spiking parvalbumin (FS-PV).9, 10, 11”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [9] Ascoli GA, Alonso-Nanclares L, Anderson SA, Barrionuevo G, Benavides-Piccione R, Burkhalter A et al. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat Rev Neurosci 2008; 9: 557–568. source

      Not checked in the free run.

    • cites [10] Karagiannis A, Gallopin T, Dávid C, Battaglia D, Geoffroy H, Rossier J et al. Classification of NPY-expressing neocortical interneurons. J Neurosci 2009; 29: 3642–3659. source

      Not checked in the free run.

    • cites [11] Perrenoud Q, Rossier J, Geoffroy H, Vitalis T, Gallopin T. . Diversity of GABAergic interneurons in layer VIa and VIb of mouse barrel cortex. Cereb Cortex 2013; 23: 423–441. source

      Not checked in the free run.

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

    Study design and conductnone given

    Primers were designed to be on two different exons of the target mRNA so as to differentiate actual transcripts from eventual genomic DNA contaminations.

    “All primers were designed to be on two different exons of the target mRNA, so as to differentiate actual transcripts from eventual genomic DNA contaminations.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    It is proposed that the secreted proteases modify the structure of the PNN and in turn could be involved in neuronal plasticity and long-term memory.

    “It is proposed that these secreted proteases modify the structure of the PNN and in turn could be involved in neuronal plasticity and long-term memory.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Recent reports have demonstrated the importance of proteases in neuronal plasticity by reshaping the PNN.

    “Recent reports have demonstrated the importance of proteases in neuronal plasticity by reshaping the PNN.3, 4, 5, 6”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [3] Huntley GW . Synaptic circuit remodelling by matrix metalloproteinases in health and disease. Nat Rev Neurosci 2012; 13: 743–757. source

      Not checked in the free run.

    • cites [4] Wang D, Fawcett J . The perineuronal net and the control of CNS plasticity. Cell Tissue Res 2012; 349: 147–160. source

      Not checked in the free run.

    • cites [5] Rivera S, Khrestchatisky M, Kaczmarek L, Rosenberg GA, Jaworski DM . Metzincin proteases and their inhibitors: foes or friends in nervous system physiology? J Neurosci 2010; 30: 15337–15357. source

      Not checked in the free run.

    • cites [6] Tsien RY . Very long-term memories may be stored in the pattern of holes in the perineuronal net. Proc Natl Acad Sci USA 2013; 110: 12456–12461. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    A scRT-mPCR assay for the simultaneous detection of 27 genes, based on the best possible multiplex set without oligonucleotide cross-reactivity, was developed.

    “A scRT-mPCR assay for the simultaneous detection of 27 genes, based on the best possible multiplex set without oligonucleotide cross-reactivity, was developed.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    More recently, peptidases have been recognized to be important actors in neuronal plasticity.

    “More recently, peptidases have been recognized to be important actors in neuronal plasticity.3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Huntley GW . Synaptic circuit remodelling by matrix metalloproteinases in health and disease. Nat Rev Neurosci 2012; 13: 743–757. source

      Not checked in the free run.

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

    Premisecitation

    MMP9 has been found to be important for the establishment of late long-term potentiation.

    “Among the >20 MMPs, MMP9 has been particularly studied and found to be important for the establishment of late long-term potentiation.5, 26”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Rivera S, Khrestchatisky M, Kaczmarek L, Rosenberg GA, Jaworski DM . Metzincin proteases and their inhibitors: foes or friends in nervous system physiology? J Neurosci 2010; 30: 15337–15357. source

      Not checked in the free run.

    • cites [26] Nagy V, Bozdagi O, Matynia A, Balcerzyk M, Okulski P, Dzwonek J et al. Matrix metalloproteinase-9 is required for hippocampal late-phase long-term potentiation and memory. J Neurosci 2006; 26: 1923–1934. source

      Not checked in the free run.

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

    Premisecitation

    The coexistence of vesicular transporters for glutamate and GABA in synaptic vesicles of GABAergic neurons was already reported.

    “This was not unexpected as the coexistence of vesicular transporters for glutamate and GABA in synaptic vesicles of GABAergic neurons was already reported.23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Fattorini G, Verderio C, Melone M, Giovedì S, Benfenati F, Matteoli et al. VGLUT1 and VGAT are sorted to the same population of synaptic vesicles in subsets of cortical axon terminals. J Neurochem 2009; 110: 1538–1546. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The originality of this work was the discovery of two distinct clusters of FS-PV cells that display different electrophysiological profiles and express different subsets of genes.

    “The originality of this work was indeed the discovery of two distinct clusters of FS-PV cells that display different electrophysiological profiles and express different subsets of genes.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Iwata et al. observed that Neprilysin was downregulated in aging and Alzheimer's disease.

    “Ten years ago, Iwata et al.27 had observed that Neprilysin was downregulated in aging and Alzheimer's disease.27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Iwata N, Tsubuki S, Takaki Y, Shirotani K, Lu B, Gerard NP et al. Metabolic regulation of brain Abeta by neprilysin. Science 2001; 292: 1550–1552. source

      Not checked in the free run.

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

    Premisecitation

    Pizzorusso et al. showed that reshaping the extracellular PNN by destroying its major constituents, chondroitin sulfate proteoglycans, with chondroitinase-ABC had a marked effect in prolonging the critical period of ocular dominance in the visual system.

    “They have shown that reshaping the extracellular PNN by destroying its major constituents, chondroitine sulfate proteoglycans with chondroitinase-ABC, had a marked effect in prolonging the critical period of ocular dominance in the visual system.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L . Reactivation of ocular dominance plasticity in the adult visual cortex. Science 2002; 298: 1248–1251. source

      Not checked in the free run.

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

    Premisecitation

    Adamts8 and Adamts15 were also identified previously in FS-PV interneurons by Nelson et al.

    “Adamts8 and Adamts15 were also identified previously in FS-PV interneurons by Nelson et al.20”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Okaty BW, Miller MN, Sugino K, Hempel CM, Nelson SB . Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons. J Neurosci 2009; 29: 7040–7052. source

      Not checked in the free run.

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

    Premisecitation

    Adamts8 and Adamts15 are two metallopeptidases that could cleave the proteoglycans aggrecan and versican, two major components of the extracellular matrix of the PNN.

    “Adamts8 and Adamts15 are two metallopeptidases that could cleave the proteoglycans aggrecan and versican, two major components of the extracellular matrix of the PNN.18, 19”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Giamanco KA, Matthews RT . Deconstructing the perineuronal net: cellular contributions and molecular composition of the neuronal extracellular matrix. Neuroscience 2012; 218: 367–384. source

      Not checked in the free run.

    • cites [19] Brocker CN, Vasiliou V, Nebert DW . Evolutionary divergence and functions of the ADAM and ADAMTS gene families. Hum Genomics 2009; 4: 43–55. source

      Not checked in the free run.

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

    Premisecitation

    Sst and FS-PV interneurons have both their embryonic origin in the medial ganglionic eminence and share many features.

    “Sst and FS-PV interneurons have both their embryonic origin in the medial ganglionic eminence and share many features.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Rudy B, Fishell G, Lee S, Hjerling-Leffler J . Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons. Dev Neurobiol 2011; 71: 45–61. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Mybpc1 was detected in most cells of the PV-MP cluster (26/39) and could be considered a surrogate marker of the PV-MP cluster.

    “Mybpc1 was detected in most of the cells of the PV-MP cluster (26/39) and could be considered as a surrogate marker of the PV-MP cluster.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    On anatomical and electrophysiological criteria, two main classes of FS-PV interneurons have previously been identified: chandelier cells and basket cells.

    “On anatomical and electrophysiological criteria, two main classes of FS-PV interneurons have previously been identified, chandelier cells that target the proximal segment of pyramids and basket cells that target soma and proximal dendrites of pyramids.9”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Ascoli GA, Alonso-Nanclares L, Anderson SA, Barrionuevo G, Benavides-Piccione R, Burkhalter A et al. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat Rev Neurosci 2008; 9: 557–568. source

      Not checked in the free run.

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

    Interpretationown data

    Our observation gives more grounds to the possibility that subpopulations of GABAergic interneurons could release glutamate, making a possible fine-tuning between inhibitory and excitatory output.

    “Our observation gives more grounds to the possibility that subpopulations of GABAergic interneurons could release glutamate making a possible fine-tuning between inhibitory and excitatory output.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Zander JF, Münster-Wandowski A, Brunk I, Pahner I, Gómez-Lira G, Heinemann U et al. Synaptic and vesicular coexistence of VGLUT and VGAT in selected excitatory and inhibitory synapses. J Neurosci 2010; 30: 7634–7645. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationown data

    Our observation that a subclass of FS-PV interneurons enwrapped in the PNN expresses three MPs led us to propose that these secreted MPs could reshape the proteoglycans of the PNN.

    “Our observation that a subclass of FS-PV interneurons enwrapped in the PNN expresses three MPs led us to propose that these secreted MPs could reshape the proteoglycans of the PNN.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    Neprilysin is considered a major β-amyloid-degrading enzyme.

    “This enzyme is considered as a major β-amyloid-degrading enzyme.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    In mice, PNN protects FS-PV interneurons against oxidative stress.

    “On the other hand it was observed in mice that PNN protects FS-PV interneurons against oxidative stress.14, 15”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Cabungcal JH, Steullet P, Morishita H, Kraftsik R, Cuenod M, Hensch TK et al. Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proc Natl Acad Sci USA 2013; 110: 9130–9135. source

      Not checked in the free run.

    • cites [15] Cabungcal JH, Steullet P, Kraftsik R, Cuenod M, Do KQ . Early-life insults impair parvalbumin interneurons via oxidative stress: reversal by N-acetylcysteine. Biol Psychiatry 2013; 73: 574–582. source

      Not checked in the free run.

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

    Premisecitation

    A prevalent hypothesis is that cognitive deficits in Alzheimer's disease are associated with altered activities of FS-PV interneurons.

    “A prevalent hypothesis is that cognitive deficits in Alzheimer's disease are associated with altered activities of FS-PV interneurons.31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K et al. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 2012; 149: 708–721. source

      Not checked in the free run.

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

    Premisecitation

    Lewis et al. have associated cognitive dysfunction in schizophrenia with altered inputs on FS-PV interneurons.

    “Lewis et al.32, 33 have also associated cognitive dysfunction in schizophrenia with altered inputs on FS-PV interneurons.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [32] Glausier JR, Fish KN, Lewis DA. . Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects. Mol Psychiatry 2014; 19: 57–67.

      Not checked in the free run.

    • cites [33] Lewis DA, Curley AA, Glausier JR, Volk DW. . Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci 2011; 35: 57–67. source

      Not checked in the free run.

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

    Premisecitation

    FS-PV interneurons are at the origin of gamma oscillation in the cortex and contribute to cognitive functions.

    “FS-PV interneurons are at the origin of gamma oscillation in the cortex and contribute to cognitive functions.29, 30”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [29] Cardin JA, Carlén M, Meletis K, Knoblich U, Zhang F, Deisseroth K et al. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 2009; 459: 663–667. source

      Not checked in the free run.

    • cites [30] Sohal VS, Zhang F, Yizhar O, Deisseroth K. . Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 2009; 459: 698–702. source

      Not checked in the free run.

47 of 47

  • The paper relies on this without support.

    Wisteria floribunda agglutinin (WFA) specifically labels the perineuronal net (PNN).

    “WFA labels specifically the PNN.”
    “By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not.”
1 of 1

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?

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.

  • A PV-Sst cell is WFA-positive despite the stated absence of PNN

    Major

    WFA is identified as a PNN marker. The reported cell positive for PV, Sst and WFA contradicts the categorical conclusion that PV cells expressing Sst are not enwrapped by PNN.

  • K-means cluster count is reported as both five and six

    Major

    The abstract says K-means produced five clusters, but the Results say k=6 gave the best separation and describe six clusters.

2 of 2

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Authors
Rossier, J., Bernard, A., Cabungcal, J.-H., Perrenoud, Q., Savoye, A., Gallopin, T., Hawrylycz, M., Cuénod, M., Do, K., Urban, A., & Lein, E. S.
Affiliations
  • Inserm (FR)
  • Allen Institute for Brain Science (US)
  • Centre Hospitalier Universitaire Vaudois (CH)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Rossier, J
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2014-12-16
Volume
20
Issue
2
Pages
154-161
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/mp.2014.162
PMC
PMC4356748
OpenAlex
W2042890282
Semantic Scholar
c26ed41efa6cb07bb37a2dbaca5ecb062fbbb1d1
Cited by
101
References
35
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 7 · 2020: 9 · 2019: 12 · 2018: 12 · 2017: 14 · 2016: 12 · 2015: 2
FWCI
4.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, other-oa)
  • IRIS (submittedVersion)
Funders
  • National Science Foundation
  • Agence Nationale de la Recherche
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (125759, 310030_135736/1, 135736, 310030)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
parvalbumin interneurons, fast-spiking interneurons, perineuronal nets, metalloproteinases, ADAMTS8, ADAMTS15, neprilysin, somatosensory cortex, interneuron subtypes, reelin, amyloid beta degradation, single-cell transcriptomics, gene expression clustering
MeSH terms
ADAMTS Proteins, Reelin Protein, Action Potentials, Animals, Animals, Newborn, Interneurons, Mice, Inbred C57BL, Parvalbumins, Neprilysin, Cluster Analysis, Patch-Clamp Techniques, Receptors, N-Acetylglucosamine, Plant Lectins, Mice, ADAM Proteins, Sensorimotor Cortex, In Vitro Techniques

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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