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Cited by 124Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionNeurogenesis and neuroplasticity mechanisms

Perineuronal Nets Regulate the Inhibitory Perisomatic Input onto Parvalbumin Interneurons and γ Activity in the Prefrontal Cortex

Open access
Carceller, Hector, Guirado, Ramon, Ripolles-Campos, Edna, Teruel-Marti, Vicent, Nacher, Juan·2020·The Journal of Neuroscience
DOI 10.1523/jneurosci.0291-20.2020PMC PMC7314408
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Abstract

Parvalbumin-expressing (PV+) interneurons play a key role in the maturation and synchronization of cortical circuitry and alterations in these inhibitory neurons, especially in the medial prefrontal cortex (mPFC), have been found in different psychiatric disorders. The formation of perineuronal nets (PNNs) around many of these interneurons at the end of the critical periods reduces their plasticity and sets their connectivity. Consequently, the presence of PNNs must have an important impact on the synaptic input and the physiology of PV+ cells. In the present study, we have found that in adult male mice, prefrontocortical PV+ cells surrounded by PNNs show higher density of perisomatic excitatory and inhibitory puncta, longer axonal initial segments (AISs), and higher PV expression when compared with PV+ cells lacking PNNs. In order to better understand the impact of PNNs on the connectivity and physiology of PV+ interneurons in the mPFC, we have digested enzymatically these structures and have found a decrease in the density of inhibitory puncta on their perisomatic region but not on the PV+ perisomatic puncta on pyramidal neurons. Moreover, extracellular recordings show that the digestion of PNNs induces a decrease in γ activity, an oscillation dependent on PV+ cells, in the mPFC of anesthetized mice. Our results suggest that the presence of PNNs enwrapping PV+ cells regulates their inhibitory input and has a potent influence on their activity. These results may be relevant for psychiatric research, given the alterations in PNNs, PV+ interneurons and their physiology described in different mental disorders. SIGNIFICANCE STATEMENT Parvalbumin-expressing (PV+) interneurons are surrounded by specializations of the extracellular matrix, the perineuronal nets (PNNs). PNNs regulate the development and plasticity of PV+ cells and, consequently, their presence must influence their synaptic input and physiology. We have found, in the adult prefrontal cortex (PFC), substantial differences in the structure and connectivity of PV+ interneurons depending on the presence of PNNs. The depletion of PNNs from the PFC has also a potent effect on the connectivity of PV+ cells and on neural oscillations that depend on these cells. These findings are relevant to understand the role of PNNs in the adult brain and in certain psychiatric disorders in which alterations in PNNs and PV+ interneurons have been described.

AI snapshot

Written from the paper’s full text.

TL;DR

In adult male mice, medial prefrontal parvalbumin interneurons wrapped by perineuronal nets differ from those without nets in PV expression, perisomatic synaptic input, and axon initial segment length. Enzymatic removal of perineuronal nets reduces inhibitory perisomatic input onto these interneurons and lowers high- and fast-gamma activity in prelimbic cortex.

Key findings

  • PV1 cells with PNNs had higher PV immunofluorescence (p = 0.0310), a positive PV–WFA intensity correlation (r = 0.5585, p < 0.0001), greater densities of VGAT+ (p = 0.046) and VGAT/PV+ (p = 0.008) perisomatic puncta, greater VGLUT1+ puncta (p = 0.031), and longer AISs (p = 0.021) than PV1 cells without PNNs; CB1r+ (p = 0.980), VGLUT2+ (p = 0.887), and VGLUT1/VGAT ratio (p = 0.142) did not differ.
  • ChABC eliminated WFA labeling across the mPFC at 2 and 4 days, with slight recovery by 6 days; analyses were performed 4 days after injection.
  • After ChABC, PV1 cells showed decreased SYN+ (p = 0.008), VGAT+ (p = 0.0162), and VGAT/PV+ (p = 0.0083) perisomatic puncta, increased AIS length (p = 0.026), and a shifted VGLUT1/VGAT ratio (p = 0.0181), while VGLUT1+ puncta (p = 0.7700), PV intensity (p = 0.694), PV+ puncta on pyramidal neurons (p = 0.3023), CamkII intensity (p = 0.7269), and neuropil puncta densities were unchanged.
  • ChABC reduced FosB expression in PV1 and pyramidal cells (both p < 0.0001) and reduced high-gamma (p = 0.003) and fast-gamma (p = 6 × 10⁻⁵) power without changing low-gamma (p = 0.65), theta–gamma modulation index (p = 0.109 high, p = 0.6754 fast), or c-Fos in PV1 (p = 0.1152) and pyramidal cells (p = 0.0812).

Methods

  • Thirty three-month-old male PV-TdT mice were used: 4 for descriptive PNN/PV1 analysis and 26 for ChABC experiments, with 14 for histology and 12 for electrophysiology.
  • Mice received bilateral stereotaxic injections of ChABC or control penicillinase into the mPFC; tissue was analyzed by fluorescence immunohistochemistry, confocal imaging, and quantification of perisomatic puncta, AIS length, PV, FosB, and c-Fos.
  • Under urethane anesthesia, local field potentials were recorded from prelimbic cortex during a tail-pinch protocol; spectral power and theta–gamma modulation index were analyzed.

Limitations

  • The paper does not include a dedicated limitations section.
  • Evident from the text: only male mice were studied, recordings were performed under anesthesia, and the main ChABC analyses used a single 4-day post-injection time point.
  • The authors note that their neuropil findings differ from another study, which they attribute possibly to cortical region, survival time, or presynaptic versus postsynaptic markers analyzed.

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

Integrity signals

Registry

Crossref · 10.1523/jneurosci.0291-20.2020

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

18 of 44 cited sources checked · 11 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    A deficit in the number of PNNs has been described in the PFC of schizophrenic and bipolar patients.

    “a deficit in the number of PNNs has been described in the PFC of schizophrenic (Mauney et al., 2013) and bipolar patients (Alcaide et al., 2019)”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites Mauney et al., 2013 source
    • cites Alcaide et al., 2019 source
  • Premisecitation

    Gamma band oscillations are inextricably tied to perisomatic inhibition.

    “a rhythm inextricably tied to perisomatic inhibition (Buzsáki and Wang, 2012)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Buzsáki and Wang, 2012 source
  • Premisecitation

    Different studies have found increased cortical plasticity after induction of a decrease in inhibitory activity, in some cases involving depletion of PNNs.

    “Supporting this idea, different studies have found an increased cortical plasticity after the induction of a decrease in inhibitory activity, in some cases involving the depletion of PNNs (Harauzov et al., 2010;Toyoizumi et al., 2013;Lensjø et al., 2017b).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Harauzov et al., 2010 source
    • cites Toyoizumi et al., 2013 source

      The Discussion (Experimental Tests; page unavailable) lists perineuronal-net removal among paradigms that reactivate adult critical-period plasticity. But the paper does not report finding increased plasticity after experimentally decreasing inhibitory activity; for the developmental critical period it studies, the Introduction instead says that maturation or enhancement of inhibition initiates plasticity. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites Lensjø et al., 2017b

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

  • Findingown data

    ChABC does not change low gamma oscillations induced by tail-pinch.

    “The power spectra of stimulated epochs revealed a decrease in g oscillations (Fig. 7C,D), both in the high (p = 0.003) and fast (p = 6 Â 10 À5 ) ranges (Fig. 7E), without significant changes in low g waves (p = 0.65).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In adult male mice, PV1 cells in the mPFC surrounded by PNNs show higher PV immunofluorescence intensity than PV1 cells lacking PNNs.

    “PV1PNN1 cells more intense than PV1PNN-cells (p = 0.0310; Fig. 1B).”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 24
  • May combine two claims. 17
  • The quote only partly states this claim. 2

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

    Premisecitation

    PV1 basket interneurons constitute the main source of perisomatic inhibition both onto excitatory and inhibitory neurons.

    “PV1 basket interneurons constitute the main source of perisomatic inhibition both onto excitatory and inhibitory neurons (Freund and Katona, 2007;Pfeffer et al., 2013)”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Freund and Katona, 2007 source
    • cites Pfeffer et al., 2013 source

      The Discussion (Functional implications; page not provided) says Pvalb cells mainly inhibit perisomatic compartments of pyramidal neurons. The Results (Interneurons targeted by Pvalb cells; page not provided) show strong inhibition of Pvalb interneurons but little or none of other interneuron classes. The claim overgeneralizes this to inhibitory neurons as a group, and the passages do not establish that their inhibition is perisomatic. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Premisecitation

    The length of the axonal initial segment (AIS) is related to neuronal maturation and to some pathologic conditions.

    “The axonal initial segment (AIS) is also a dynamic structure, the length of which is related to neuronal maturation (Gutzmann et al., 2014;Bolós et al., 2019) and also to some pathologic conditions (Kuba et al., 2010;Baalman et al., 2013;Harty et al., 2013).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Gutzmann et al., 2014 source
    • cites Bolós et al., 2019 source
    • cites Kuba et al., 2010 source

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

    Study design and conductcitation

    Images were processed using previously validated macros.

    “Images were processed using previously validated macros (Guirado et al., 2018).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Guirado et al., 2018 source

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

    Premisecitation

    ChABC treatment promotes neuronal plasticity in different neocortical regions, such as the visual and auditory cortices.

    “This treatment promotes neuronal plasticity in different neocortical regions, such as the visual (Pizzorusso et al., 2002) and auditory cortices (Happel et al., 2014).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Pizzorusso et al., 2002 source
    • cites Happel et al., 2014 source

      The paper supports enhanced plasticity following extracellular-matrix removal in the auditory cortex, but its auditory-cortex experiments used hyaluronidase (HYase), not ChABC (Enhanced Reversal Learning of FM Discrimination After ECM Removal; Local Removal of the ECM in Adult ACx and Its Temporal Reappearance). The visual-cortex portion of the citing sentence is attributed to a different citation and is not judged here. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    FosB is linked to long-term activity levels.

    “Since FosB has been linked to long-term activity levels (Nestler, 2015)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Nestler, 2015 source

      Section 3 (page unavailable) links sustained neural activity to full-length FosB levels, but only as a possibility following repeated fluoxetine treatment in the nucleus accumbens; it says further work is needed to test that explanation. The unqualified claim that FosB is linked to long-term activity levels is broader than this tentative account. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Experience-dependent accumulation of exogenous OTX2 is necessary for the formation of PNNs and critical period closure in the visual cortex.

    “On the other hand, an experience-dependent accumulation of exogenous OTX2, a homeoprotein commonly bound to PNNs and PV1 cells in the mPFC (Lee et al., 2017), is necessary for the formation of PNNs and critical period closure in the visual cortex (Sugiyama et al., 2008).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Sugiyama et al., 2008 source
    • cites Lee et al., 2017 source

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

    Premisecitation

    Alterations of prefrontocortical PV1 interneurons and PNNs have been described in schizophrenia or bipolar disorder.

    “in which alterations of prefrontocortical PV1 interneurons and PNNs have been described (Mauney et al., 2013;Enwright et al., 2016;Alcaide et al., 2019).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites Mauney et al., 2013 source
    • cites Enwright et al., 2016 source
    • cites Alcaide et al., 2019 source

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

    Premisecitation

    A sensory paradigm can induce a synchronous activated state in the prefrontal neuronal circuitry and elicit theta oscillations with nested gamma activity.

    “We used a sensory paradigm to induce a synchronous activated state in the prefrontal neuronal circuitry and, thus, elicit u oscillations with a nested g activity (Sohal et al., 2009)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Sohal et al., 2009 source

      The paper reports that rhythmic light stimulation induced theta- or gamma-frequency firing in pyramidal neurons, and it also tested prefrontal pyramidal neurons (section labeled Abstract; page unavailable). It does not show that a sensory paradigm induced a synchronous activated prefrontal state or theta oscillations with gamma activity nested within them; theta and gamma were applied as separate stimulation patterns. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the cortex, dendritic inhibition on PV1 cells is mainly provided by somatostatin interneurons, whereas the main source for perisomatic inhibition comes from other PV1 cells.

    “Moreover, in the cortex, dendritic inhibition on PV1 cells is mainly provided by somatostatin1 interneurons, whereas the main source for perisomatic inhibition comes from other PV1 cells (Pfeffer et al., 2013).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Pfeffer et al., 2013 source

      The Results section (“Comparing inhibition mediated by distinct interneurons”; page unavailable) says Pvalb cells are the main source of inhibition onto other Pvalb cells, while Sst cells also inhibit them. The Discussion (“Functional implications”; page unavailable) describes Sst dendritic and Pvalb perisomatic targeting on pyramidal cells, not on Pvalb cells. The claimed locations of those inputs on Pvalb cells are therefore unsupported. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Interpretationreasoning

    Theta waves are maintained, probably by an external input, while local gamma oscillations reduce their presence by a putative imbalance of excitatory-inhibitory activity as a consequence of the loss of perisomatic synapses on PV cells.

    “Based on these results, we hypothesize that u waves are maintained, probably by an external input (Siapas et al., 2005;Sirota et al., 2008), while the local g oscillations reduce their presence by a putative imbalance of the excitatory-inhibitory activity as a consequence of the loss of perisomatic synapses on PV cells.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Siapas et al., 2005 source
    • cites Sirota et al., 2008 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Theta oscillations with nested gamma activity are a characteristic functional pattern depending on synaptic inhibition onto PV-expressing cells.

    “a characteristic functional pattern depending on synaptic inhibition onto PV-expressing cells (Buzsáki and Wang, 2012).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Buzsáki and Wang, 2012 source

      In “Brain-Wide Synchronization of Gamma Oscillations by Slower Rhythms” (page unavailable), the paper documents theta–gamma coupling and proposes that basket cells contribute because other interneurons, entrained by slower rhythms, inhibit them. It presents this mechanism as a hypothesis, not an established dependency on synaptic inhibition onto PV-expressing cells. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • The quote only partly states this claim.

    Findingown data

    ChABC decreases VGAT+ puncta in both low PV and high PV PV1 cell populations.

    “we split the PV1 cells into”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Findingown data

    The AIS length is longer in PV1 cells surrounded by PNNs than in PV1 cells lacking PNNs.

    “As a structural characteristic of the maturational stage, we studied the length of the AIS using AnkG immunohistochemistry (Fig. 1J) and found that it was significantly shorter in the PV1PNN-cells (p = 0.021; Fig. 1K).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    PV1 cells surrounded by PNNs have a higher density of perisomatic VGLUT1+ excitatory puncta than PV1 cells lacking PNNs.

    “we found a significant decrease in the density of puncta from cortical origin (VGLUT11; p = 0.031; Fig. 1H), but not in that of puncta from extracortical origin (VGLUT21; p = 0.887; Fig. 2C,D) in PV1PNN-cells.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    ChABC treatment increases AIS length in PV1 cells.

    “We also studied the effects of PNNs depletion on the AIS length (Fig. 4F) and found a significant increase as a consequence of ChABC injection (p = 0.026; Fig. 4G).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    ChABC treatment induces a reduction in the density of inhibitory perisomatic puncta from PV1 cells onto PV1 cells, rendering a VGLUT1/VGAT ratio similar to that found in PV1PNN- cells in control animals.

    “We found that ChABC treatment induces specifically a reduction in the density of inhibitory perisomatic puncta from PV1 cells onto PV1 cells, rendering a VGLUT1/VGAT ratio similar to that found in the PV1PNN-cells in control animals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    ChABC treatment induces a decrease in the density of inhibitory but not excitatory puncta on the perisomatic region of PV1 cells.

    “Graphs showing the ChABC induced decrease in the density of inhibitory but not excitatory puncta on the perisomatic region of PV1 cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After ChABC treatment in the PFC, gamma oscillations decrease while theta-gamma coupling is maintained.

    “After ChABC treatment in the PFC, our results showed a decrease of g oscillations, maintaining the u -g coupling.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    PV1 basket cells show a fast and non-adapting firing pattern, providing a synchronized modulation of cortical activity through the regulation of gamma oscillations.

    “The PV1 basket cells show a fast and non-adapting firing pattern, providing a synchronized modulation of cortical activity through the regulation of g oscillations (Kubota, 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kubota, 2014 source

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The acquiring conditions were maintained throughout all imaging sessions to compare fluorescence intensity between samples.

    “The acquiring conditions were maintained throughout all the imaging sessions to compare the fluorescence intensity between samples.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    PNNs are formed during development in an activity-dependent manner.

    “PNNs are formed during development (Brückner et al., 2000) in an activity-dependent manner (Dityatev et al., 2007).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Brückner et al., 2000

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

    • cites Dityatev et al., 2007 source

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

    Premisecitation

    PNNs have an important role in the maturation and stabilization of the connectivity of PV1 interneurons in critical periods such as those of the visual and auditory systems.

    “The PNNs have an important role in the maturation and stabilization of the connectivity of PV1 interneurons in critical periods such as those of the visual and auditory systems (Pizzorusso et al., 2002;Cisneros-Franco and de Villers-Sidani, 2019).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Pizzorusso et al., 2002 source
    • cites Cisneros-Franco and de Villers-Sidani, 2019 source

      Checked before — its earlier verdict is held back until a new check runs.

  • May combine two claims.

    Interpretationown data

    The presence of PNNs enwrapping PV1 cells regulates their inhibitory input and has a potent influence on their activity.

    “Our results suggest that the presence of PNNs enwrapping PV1 cells regulates their inhibitory input and has a potent influence on their activity.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Removal of PNNs is linked to decreased inhibition in the visual cortex.

    “A recent study in the visual cortex (Lensjø et al., 2017b) has linked the removal of PNNs to a decreased inhibition, suggesting that ChABC treatment may reset the connectivity to a juvenile-like state.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lensjø et al., 2017b

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

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

    Premisecitation

    The expression level of PV can be used to classify PV1 cells into different subpopulations regarding their activity and connectivity patterns.

    “the expression level of PV can be used to classify them in different subpopulations regarding their activity and connectivity patterns”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Donato et al., 2013 source
    • cites Donato et al., 2015 source

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

    Premisecitation

    High PV expression hippocampal PV1 cells receive less inhibition and more excitation inputs than low PV expression cells in their dendritic compartment.

    “A previous report, focused on hippocampal PV1 cells, described that high PV expression cells receive less inhibition and more excitation inputs than low PV expression cells, but in their dendritic compartment (Donato et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Donato et al., 2013 source

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

    Premisecitation

    The appearance of PNNs surrounding PV1 cells marks an abrupt reduction of neuronal plasticity at the end of the critical periods.

    “The appearance of PNNs surrounding PV1 cells marks an abrupt reduction of neuronal plasticity at the end of the critical periods, temporal windows of enhanced neuronal plasticity that occur during the latest stages of development (Hensch, 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hensch, 2005 source

  • May combine two claims.

    Interpretationreasoning

    The basal activity of PV1 cells and pyramidal neurons is reduced after PNN depletion.

    “these data support our electrophysiology results, indicating that the basal activity, not only of PV1 cells but also of pyramidal neurons is reduced.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The appearance of PNNs coincides with the maturation of PV1 cells and the decrease of plasticity levels in neocortical regions, hippocampus, and amygdala.

    “Although critical periods are specific for different systems and have a different time lines, the appearance of PNNs coincides with the maturation of PV1 cells and the decrease of plasticity levels, not only in neocortical regions (Pizzorusso et al., 2002;Ueno et al., 2018), but also in the hippocampus (Bukalo et al., 2001) and the amygdala (Gogolla et al., 2009).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Pizzorusso et al., 2002 source
    • cites Ueno et al., 2018 source
    • cites Bukalo et al., 2001 source

  • May combine two claims.

    Interpretationcitation

    Dendritic inhibition may be decreased in high PV expression cells and may be more sensitive to stimuli such as environmental enrichment.

    “By contrast, dendritic inhibition may be decreased in these cells and may be more sensitive to stimuli, such as environmental enrichment (Donato et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Donato et al., 2013 source

  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Interpretationreasoning

    High PV expression cells may receive higher perisomatic inhibition, stabilized by PNNs.

    “Therefore, we hypothesize that high PV expression cells may receive higher perisomatic inhibition, stabilized by PNNs.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    A recent report found a decrease in puncta expressing inhibitory markers after ChABC treatment in the primary visual cortex.

    “A recent report has also found a decrease in puncta expressing inhibitory markers after ChABC treatment in the primary visual cortex (Lensjø et al., 2017a).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lensjø et al., 2017a

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

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationcitation

    These results may be relevant for understanding the etiopathology of psychiatric disorders such as schizophrenia or bipolar disorder.

    “These results may be relevant for our understanding of the etiopathology of psychiatric disorders, such as schizophrenia or bipolar disorder”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    There exist two subpopulations of PV1 cells in the mPFC, defined by the presence of PNNs, with differential PV expression and perisomatic connectivity.

    “Taken together, our results suggest the existence of two subpopulations of PV1 cells in the mPFC, defined by the presence of PNNs, with differential PV expression and perisomatic connectivity.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Increase in AIS length is related to the maturation of other neuronal types.

    “Since the increase in AIS length has been previously related to the maturation of other neuronal types (Sammons et al., 2018;Bolós et al., 2019)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Sammons et al., 2018 source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites Bolós et al., 2019 source

  • May combine two claims.

    Interpretationreasoning

    The presence of PNNs is a feature of mature PV1 cells, which may have a different role in the PV circuitry from those without PNNs.

    “our data support the hypothesis of the presence of PNNs as a feature of mature PV1 cells, which may have a different role in the PV circuitry from those without PNNs.”
    Quote in the paperSubstantial claim
36 of 36

  • The paper relies on this without support.

    The effects of ChABC on PNNs and neuronal connectivity remain unexplored in the medial prefrontal cortex.

    “The effects of ChABC have been extensively studied in sensory systems but remain unexplored in high-order areas such as the medial prefrontal cortex (mPFC), whose dysfunction underlies different psychiatric disorders.”

  • The paper relies on this without support.

    The impact of the presence of PNNs on the AIS of PV1 cells remains to be explored.

    “Nevertheless, this parameter has only been studied on excitatory neurons and the impact of the presence of PNNs on the AIS of PV1 cells still remains to be explored.”

  • The paper relies on this without support.

    ChABC treatment specifically digests PNNs without affecting other extracellular matrix components or cellular processes.

    “After ChABC treatment in the PFC, our results showed a decrease of g oscillations, maintaining the u -g coupling.”

  • The paper relies on this without support.

    The density of perisomatic puncta expressing inhibitory markers reflects the strength or number of functional inhibitory synapses onto PV1 cells.

    “Our results show a positive correlation of PV expression and the density of perisomatic inhibitory puncta onto PV1 cells.”

  • The paper relies on this without support.

    PV fluorescence intensity is a valid measure of PV expression level in PV1 cells.

    “We also describe a positive correlation between PNNs and PV expression”

  • The paper relies on this without support.

    WFA labeling specifically identifies PNNs.

    “representative immunostaining of the expression of PV and WFA in PrL”
6 of 6

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Authors
Carceller, H., Guirado, R., Ripolles-Campos, E., Teruel-Marti, V., & Nacher, J.
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2020-05-26
Volume
40
Issue
26
Pages
5008-5018
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.0291-20.2020
PMC
PMC7314408
OpenAlex
W3031913802
Cited by
112
References
42
Citations by year
2026: 22 · 2025: 18 · 2024: 18 · 2023: 17 · 2022: 18 · 2021: 19
FWCI
6.18
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion)
Funders
  • Ministerio de Ciencia, Innovación y Universidades (BFU2016-77691-C2, RTI2018‐098269‐B‐I00, IJCI-2016-27758, FPU15, RTI2018, SAF2015-68436-R)
  • Ministerio de Economía y Competitividad (SAF2015-68436-R, C2-2-P)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
perineuronal nets, parvalbumin interneurons, medial prefrontal cortex, perisomatic inhibition, gamma oscillations, axon initial segment, extracellular matrix, interneuron connectivity, mental illness, cortical circuits, adult brain plasticity, critical period, pyramidal neurons, extracellular recording, mice
MeSH terms
Animals, Extracellular Matrix, Interneurons, Male, Mice, Inbred C57BL, Neuronal Plasticity, Parvalbumins, Prefrontal Cortex, Mice, Gamma Rhythm

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 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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