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Cited by 220Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionNeurogenesis and neuroplasticity mechanisms

Four Unique Interneuron Populations Reside in Neocortical Layer 1

Open access
Schuman, Benjamin, Machold, Robert P., Hashikawa, Yoshiko, Fuzik, János, Fishell, Gord J., Rudy, Bernardo·2019·The Journal of Neuroscience
DOI 10.1523/jneurosci.1613-18.2018PMC PMC6325270
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Abstract

Sensory perception depends on neocortical computations that contextually adjust sensory signals in different internal and environmental contexts. Neocortical layer 1 (L1) is the main target of cortical and subcortical inputs that provide “top-down” information for context-dependent sensory processing. Although L1 is devoid of excitatory cells, it contains the distal “tuft” dendrites of pyramidal cells (PCs) located in deeper layers. L1 also contains a poorly characterized population of GABAergic interneurons (INs), which regulate the impact that different top-down inputs have on PCs. A poor comprehension of L1 IN subtypes and how they affect PC activity has hampered our understanding of the mechanisms that underlie contextual modulation of sensory processing. We used novel genetic strategies in male and female mice combined with electrophysiological and morphological methods to help resolve differences that were unclear when using only electrophysiological and/or morphological approaches. We discovered that L1 contains four distinct populations of INs, each with a unique molecular profile, morphology, and electrophysiology, including a previously overlooked IN population (named here “canopy cells”) representing 40% of L1 INs. In contrast to what is observed in other layers, most L1 neurons appear to be unique to the layer, highlighting the specialized character of the signal processing that takes place in L1. This new understanding of INs in L1, as well as the application of genetic methods based on the markers described here, will enable investigation of the cellular and circuit mechanisms of top-down processing in L1 with unprecedented detail. SIGNIFICANCE STATEMENT Neocortical layer 1 (L1) is the main target of corticocortical and subcortical projections that mediate top-down or context-dependent sensory perception. However, this unique layer is often referred to as “enigmatic” because its neuronal composition has been difficult to determine. Using a combination of genetic, electrophysiological, and morphological approaches that helped to resolve differences that were unclear when using a single approach, we were able to decipher the neuronal composition of L1. We identified markers that distinguish L1 neurons and found that the layer contains four populations of GABAergic interneurons, each with unique molecular profiles, morphologies, and electrophysiological properties. These findings provide a new framework for studying the circuit mechanisms underlying the processing of top-down inputs in neocortical L1.

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Written from the paper’s full text.

TL;DR

Using genetic, electrophysiological, and morphological methods in mouse barrel cortex, this study identifies four distinct GABAergic interneuron populations in neocortical layer 1: NDNF/NPY NGFCs, NDNF/non-NPY canopy cells, α7 nAChR cells, and VIP cells. The previously overlooked canopy cells account for ~40% of L1 interneurons and differ from NGFCs in morphology and connectivity.

Key findings

  • L1 contains four molecularly defined interneuron populations: NDNF/NPY (NGFCs), NDNF/non-NPY (canopy cells), α7 nAChR cells, and VIP cells. NDNF labeling captured ~70% of L1 INs (66.8 ± 1.3%, n = 4 mice); NDNF/NPY cells were ~40% of the NDNF population (~30% of L1), NDNF/non-NPY cells ~60% (~40% of L1), and non-NDNF cells ~30% of L1, split into ~30% VIP (~10% of L1) and ~70% α7 cells (~20% of L1).
  • Electrophysiologically, NGFCs were late-spiking (time to first spike 750.1 ± 28.6 ms; adaptation index 1.01 ± 0.02), VIP cells had high input resistance (351.1 ± 21.1 MΩ) and strong adaptation (0.44 ± 0.05), and α7 cells had a prominent near-threshold depolarizing hump (17.3 ± 0.5 mV) and larger sag (21.5 ± 1.6%). Canopy cells were non-LS with moderate adaptation (0.83 ± 0.02).
  • Morphologically, NGFC and canopy axons were largely confined to L1, but canopy axons were biased to the upper half of L1 (L1a p = 3.3e-4; L1b p = 5.8e-4), whereas NGFC axons occupied the whole layer. α7 and VIP cells had descending collaterals; α7 cells were multipolar and VIP cells bipolar (p = 0.0047), with different soma sizes (p = 0.0012).
  • Connectivity differed: NGFC→L2 PC connection probability was 72% (13/18) versus 18% for canopy cells (8/45; p = 7.2e-5); NGFC IPSPs were larger (p = 7.6e-4) and had a significant GABA_B component (p = 0.031), while canopy IPSPs did not. NGFC→canopy IPSPs were stronger than canopy→NGFC IPSPs (p = 0.012).

Methods

  • Genetic labeling and histology in male and female mice (P21–P53; mean age P30.3 ± 0.3), using NPY-hrGFP, NDNF-ires-Cre, Htr3a-ires-Flpo, VIP/CCK lines, viral tdTomato reporter, FISH/IHC, and α-bungarotoxin labeling.
  • Whole-cell current-clamp recordings in barrel field of primary somatosensory cortex slices, with biocytin filling for post hoc morphology; paired recordings between L1 INs and L2 PCs; intrinsic properties measured from 1-s current injections.
  • Unsupervised cluster analysis (Ward’s method) on 82 cells using 11 electrophysiological parameters; statistics included Kruskal-Wallis with Dunn’s/Šidák correction, Mann-Whitney U, Fisher’s exact, and Wilcoxon signed-rank tests.

Limitations

  • Stated: further studies may reveal additional diversity within the described groups; it is not yet clear how transcriptomic clustering corresponds to specific functional cell properties; some comparative area data are not shown.
  • Stated/evident: some cells lacked complete electrophysiological analysis (n values are minimum), and cells could be used either for reconstructions or α-btx staining, not both; liquid junction potential was not corrected and cells with access resistance >35 MΩ were excluded.
  • Evident: findings are from in vitro mouse barrel cortex slices at P21–P53, so age/area generality and in vivo circuit or behavioral roles are not established here; no sex-specific analyses are reported despite use of male and female mice.

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

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Crossref · 10.1523/jneurosci.1613-18.2018

Cites

88 of 88 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 43 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    L1 contains a previously overlooked interneuron population named canopy cells.

    “including a previously overlooked IN population (named here”
    Quote in the paperSubstantial claim
  • Findingown data

    Canopy cells represent 40% of L1 interneurons.

    “including a previously overlooked IN population (named here”
    Quote in the paperSubstantial claim
  • Findingown data

    Neocortical layer 1 contains four distinct populations of GABAergic interneurons.

    “We discovered that L1 contains four distinct populations of INs, each with a unique molecular profile, morphology, and electrophysiology, including a previously overlooked IN population (named here”
    • Also stated in: § Significance Statement · plain
      “We identified markers that distinguish L1 neurons and found that the layer contains four populations of GABAergic interneurons, each with unique molecular profiles, morphologies, and electrophysiological properties.”
    • Also stated in: § Significance Statement · plain
      “We identified markers that distinguish L1 INs and found that L1 contains four IN populations, each with unique molecular profiles, morphologies, and electrophysiological properties.”
    Quote in the paperSubstantial claim
  • Findingown data

    Cells strongly labeled for α7 nAChRs were almost exclusively restricted to L1.

    “Remarkably, although sparse, cells strongly labeled for ␣7 nAChRs (hereafter called ␣7 cells) were almost exclusively restricted to L1 (Fig. 2).”
    Quote in the paperSubstantial claim
  • Findingown data

    In the NPY-hrGFP mouse line, more than 90% of GFP-positive cells in L1 (153/165 recorded NPY+ cells) had the late-spiking firing pattern characteristic of neurogliaform cells.

    “We found that Ͼ90% of the GFP-positive cells in L1 (n ϭ 153/165 recorded NPYϩ cells; Fig. 1B) had the LS firing pattern characteristic of NGFCs.”
    Quote in the paperSubstantial claim
  • May combine two claims. 36
  • Classified as probably not a substantial claim. 6

  • May combine two claims.

    Findingown data

    Each of the four L1 interneuron populations has a unique molecular profile, morphology, and electrophysiological properties.

    “We discovered that L1 contains four distinct populations of INs, each with a unique molecular profile, morphology, and electrophysiology, including a previously overlooked IN population (named here”
    • Also stated in: § Significance Statement · plain
      “We identified markers that distinguish L1 neurons and found that the layer contains four populations of GABAergic interneurons, each with unique molecular profiles, morphologies, and electrophysiological properties.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The axon of canopy cells extends further from the soma (p = 0.021) and is less tortuous than the axon of NGFCs (p = 0.0024).

    “The axon of the canopy cells extends further from the soma (Fig. 6D; p ϭ 0.021; Mann-Whitney U test) and is less tortuous than the axon of NGFCs (Fig. 6E; p ϭ 0.0024; Mann-Whitney U test).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The experimental observer could distinguish cell types with a high degree of certainty using a few key properties: long delay to first spike and lack of adaptation at threshold of NDNF/NPY cells, active depolarizing hump at threshold for α7 cells, onset spikes at threshold without active depolarizing hump for NDNF/non-NPY cells, and high input resistance and strong adaptation for VIP cells.

    “The experimental observer could distinguish cell types with a high degree of certainty using a few key properties that distinguished among cells: the long delay to first spike and lack of adaptation at threshold of NDNF/NPY cells, the active depolarizing hump at threshold for the ␣7 cells, the presence of onset spikes at threshold without an active depolarizing hump for the NDNF/non-NPY cells, and”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cortical NDNF expression is highly enriched in L1 INs and has no overlap with PV, SST, and VIP.

    “Using ISH, we confirmed that cortical NDNF expression is highly enriched in L1 INs (Fig. 2), having no overlap with the other major IN classes (PV, SST, and VIP).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    L1 VIP cells resemble bipolar VIP INs in L2/3, with a descending axon that projects through the cortical column.

    “L1 VIP cells resemble the bipolar VIP INs in L2/3, with a descending axon that projects through the cortical column (Lee et al., 2010;Pro ¨nneke et al., 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Lee et al., 2010

      Not checked in the free run.

    • cites Pro ¨nneke et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The NPY population comprised a subset of L1 INs within the NDNF population, dividing NDNF cells into NPY-positive and NPY-negative groups.

    “By incorporating the NPY-hrGFP reporter into this approach, we found that the NPY population comprised a subset of L1 INs within the NDNF population such that NDNF cells could be divided into NPY-positive and NPY-negative groups (Fig. 2F ).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The NDNF/non-NPY cells (canopy cells) resemble NGFCs in having an elongated horizontal axonal arbor largely confined to L1, but show several significant morphological differences from NGFCs.

    “The NDNF/non-NPY cells (hereafter called canopy cells, as explained below) resemble NGFCs in having an elongated horizontal axonal arbor largely confined to L1; however, they show several significant morphological differences from NGFCs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The dendritic arbor of canopy cells is wider than that of NGFCs (p = 0.0023) and branches less (p = 0.0072).

    “The dendritic arbor of the canopy cells is wider than that of NGFCs (Fig. 6A; p ϭ 0.0023; Mann-Whitney U test) and branches less (Fig. 6B; p ϭ 0.0072, respectively; Mann-Whitney U test).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Most NDNF/NPY cells (92% in the present dataset) had a late-spiking firing pattern near threshold and non-adapting or even accelerating repetitive firing.

    “Most NDNF/NPY cells (92% in the present dataset) had a LS firing pattern near threshold and non-adapting or even accelerating repetitive firing;”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    NDNF/NPY cells (NGFCs) had a NGFC morphology with short dendrites and a wider dense axonal arbor, which differs from NGFCs in other layers by often extending horizontally across several columns.

    “NDNF/NPY cells (hereafter called NGFCs) had a NGFC morphology with short dendrites and a wider dense axonal arbor, which differs from NGFCs in other layers by often extending horizontally across several columns, as described previously (Hestrin and Armstrong, 1996;Zhou and Hablitz, 1996b;Kubota et al., 2011;Jiang et al., 2013Jiang et al., , 2015;;Tremblay et al., 2016).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Hestrin and Armstrong, 1996

      Not checked in the free run.

    • cites Zhou and Hablitz, 1996b

      Not checked in the free run.

    • cites Kubota et al., 2011

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The axonal arbor of the two NDNF populations had a different distribution within L1: NGFC axons tend to occupy the whole layer, whereas canopy cell axons are strongly biased toward the upper half of L1 and are rarely found in L2.

    “Interestingly, we also found that the axonal arbor of the two NDNF populations had a different distribution within L1: whereas the axon of NGFCs tends to occupy the whole layer, the axon of the canopy cells is strongly biased toward the upper half of L1, and is rarely found in L2 (Fig. 4C,D; L1a: p ϭ 3.3e-4; L1b: p ϭ 5.8e-4; Mann-Whitney U test).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Approximately 30% of non-NDNF INs (and thus 10% of L1) were VIP cells, a marker that did not overlap with NDNF.

    “Approximately 30% of non-NDNF INs (and thus 10% of L1) were VIP cells, a marker that did not overlap with NDNF (Fig. 2C)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    VIP cells in L1 have very high input resistances and adapt the most (input resistance: 351.1 MΩ ± 21.1 vs 141.9 ± 6.6 and 141.6 ± 10.8 for NDNF/non-NPY and α7; adaptation index: 0.44 ± 0.05 vs 0.83 ± 0.02 and 0.60 ± 0.03).

    “VIP cells in L1 have very high input resistances and adapt the most (input resistance: 351.1 M⍀ Ϯ 21.1 compared with 141.9 Ϯ 6.6 and 141.6 Ϯ 10.8 for the NDNF/non-NPY and ␣7 populations, respectively; adaptation index: 0.44 Ϯ 0.05 compared with 0.83 Ϯ 0.02 and 0.60 Ϯ 0.03 for the NDNF/non-NPY and ␣7 populations respectively; for statistics, see Table 3)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    NDNF/NPY INs account for about 40% of the NDNF population (mean ± SEM = 40.8 ± 0.7%, n = 4 mice) and thus about 30% of L1.

    “NDNF/NPY INs account for ϳ40% of the NDNF population (mean Ϯ SEM ϭ 40.8 Ϯ 0.7%, n ϭ 4 mice and thus ϳ30% of L1)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Peak axonal density is about 65% larger and interbouton distance is smaller for NGFCs, resulting in a twofold difference in bouton density for the two cell types.

    “Furthermore, peak axonal density is ϳ65% larger (Fig. 6G; p ϭ 0.0152; Mann-Whitney U test) and the interbouton distance is smaller (Fig. 6F; p ϭ 0.0016; Mann-Whitney U test) for NGFCs, resulting in a twofold difference in bouton density for the two cell types.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The NDNF/non-NPY population accounts for 60% of the NDNF population and thus about 40% of L1.

    “and the NDNF/non-NPY population for 60% (and thus ϳ40% of L1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The descending axonal collaterals of L1 VIP cells branch in L5A and continue into L5B, often reaching layer 6.

    “The descending axonal collaterals of L1 VIP cells branch in L5A, a cortical sublayer that often receives projections from similar sources as L1 and then continue into L5B, often reaching layer 6 (Figs. 4, 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The α7 cell is multipolar and the VIP cell is bipolar.

    “Inset shows the magnified somatodendritic profile of the ␣7 and VIP cells showing that the ␣7 cell is multipolar and the VIP cell is bipolar.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Consistent with observations in other studies, robust unitary GABAB responses are found in L1 NGFC connections with L2 PCs, representing a significant proportion of the PSP elicited by NGFC stimulation (p = 0.031).

    “Consistent with observations in other studies, we find robust unitary GABA B re-sponses in L1 NGFC connections with L2 PCs, representing a significant proportion of the PSP elicited by NGFC stimulation (Fig. 8 B, E; p ϭ 0.031; Wilcoxon signed-rank test).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Like VIP cells, α7 cells have one or more vertically descending axonal collaterals that go deep into the column; they usually branch in L5A but often terminate there, in contrast to VIP cells.

    “Like VIP cells, ␣7 cells have one or more vertically descending axonal collaterals that go deep into the column.They usually branch in L5A, but often terminate there, in contrast to VIP cells (Figs. 4A, 5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The two NDNF populations have similar morphologies but very distinct electrophysiological properties.

    “The two NDNF populations have similar morphologies but very distinct electrophysiological properties.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    L1 VIP cells resemble bipolar VIP cells in L2-6, but their bipolar dendrite is oriented horizontally.

    “Conversely, although L1 VIP cells resemble bipolar VIP cells in L2-6, their bipolar dendrite is oriented horizontally (Fig. 4), whereas the dendritic trees of bipolar VIP INs in other layers are narrow and oriented vertically, crossing several layers in either direction (Lee et al., 2013;Pro ¨nneke et al., 2015).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Lee et al., 2013

      Not checked in the free run.

    • cites Pro ¨nneke et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    NGFCs and canopy cells differ in their connectivity to L2 PCs and each other, supporting the notion that they represent distinct IN subtypes.

    “The two NDNF populations, NGFCs and canopy cells, also differ in their connectivity to L2 PCs and each other, supporting the notion that they represent distinct IN subtypes (Figs. 8, 9).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    NGFCs and canopy cells were reciprocally connected and the probability of detecting connections was high in both directions.

    “NGFCs and canopy cells were reciprocally connected and the probability of detecting connections was high in both directions (Fig. 9A).”
    Quote in the paperSubstantial claim

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

    Findingown data

    Three additional non-NDNF cells were confirmed as α7 nAChR-expressing but were not included in the analysis due to partial electrophysiological data.

    “Three additional non-NDNF cells were also confirmed as ␣7 nAChR-expressing, but only partial electrophysiological data were collectedfromthesecellsandtheywerethereforenotincludedinthisanalysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Canopy cells and α7 neurons resemble each other electrophysiologically but are distinguishable morphologically.

    “Conversely, canopy cells and ␣7 neurons resemble each other electrophysiologically (Fig. 3) but are distinguishable morphologically.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    NGFCs and VIP INs are present in other layers, but have unique properties in L1 of potential physiological significance.

    “NGFCs and VIP INs are present in other layers, but have unique properties in L1 of potential physiological significance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Only IPSPs elicited by NGFCs have a significant GABA B component, whereas those elicited by canopy cells do not.

    “Only IPSPs elicited by NGFCs had a significant GABA B component ( p ϭ 0.031, Wilcoxon signed-rank test).”
    • Also stated in: § Sublaminar structure of layer 1 · plain
      “showing a prominent GABA B component elicited by NGFCs, but not canopy cells.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Neurogliaform cells mediate long-lasting GABA_A and GABA_B inhibition of pyramidal cells and have a late-spiking firing pattern when depolarized to near threshold.

    “Previous studies of L1 INs agree that an important component of this population is neurogliaform cells (NGFCs), INs that mediate long-lasting GABA A and GABA B inhibition of PCs and have a late-spiking (LS) firing pattern when depolarized to near threshold membrane potentials (Chu et al., 2003;Tama ´s et al., 2003;Overstreet-Wadiche and McBain, 2015;Tremblay et al., 2016).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Chu et al., 2003

      Not checked in the free run.

    • cites Tama ´s et al., 2003

      Not checked in the free run.

    • cites Overstreet-Wadiche and McBain, 2015

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    VIP interneurons are the major population of L2/3 interneurons, accounting for 35% of interneurons in these layers, but are infrequent in L1.

    “VIP INs are the major population of L2/3 INs, accounting for 35% of the INs in these layers (Tremblay et al., 2016), but are infrequent in L1 (Lee et al., 2010).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Tremblay et al., 2016

      Not checked in the free run.

    • cites Lee et al., 2010

      Not checked in the free run.

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

    Premisecitation

    Several studies have included a substantial proportion of unclassified L1 interneurons.

    “Furthermore, several studies have included a substantial proportion of unclassified cells (Table 1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Table 1

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The active depolarization in α7 cells is likely mediated by a Ca2+ conductance similar to that in thalamic relay neurons because it is blocked by the T-channel blocker TTA-P2.

    “This active depolarization resembles the Ca 2ϩ spike observed in thalamic relay neurons (Llina ´s and Jahnsen, 1982;Jahnsen and Llina ´s, 1984;McCormick and Huguenard, 1992) and is likely mediated by a similar Ca 2ϩ conductance because it is blocked by the T-channel blocker TTA-P2 (3 M; data not shown).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Llina ´s and Jahnsen, 1982

      Not checked in the free run.

    • cites Jahnsen and Llina ´s, 1984

      Not checked in the free run.

    • cites McCormick and Huguenard, 1992

      Not checked in the free run.

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

    Study design and conductnone given

    The intrinsic properties of cells with access resistances greater than 35 MΩ were not analyzed.

    “The intrinsic properties of cells with access resistances Ͼ35 M⍀ were not analyzed.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The liquid junction potential was not corrected in the recordings.

    “All recordings were performed in currentclamp conditions using the whole-cell configuration in brain slices and the liquid junction potential was not corrected.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Most L1 interneurons are non-VIP 5HT3aR cells, a heterogeneous population with poorly characterized diversity.

    “Therefore, most L1 INs are non-VIP 5HT3aR cells, a heterogeneous interneuron population with a poorly characterized diversity (Lee et al., 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lee et al., 2010

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Closer examination of these data indicated that a substantial fraction of cells clustered within the NDNF/Cxcl14 category were actually non-NDNF expressing and likely included the α7 cells reported here.

    “However, closer examination of these data indicated that a substantial fraction of cells clustered within the NDNF/Cxcl14 category were actually non-NDNF expressing and likely included the ␣7 cells reported here.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Comparative histological analysis indicates that the same populations are present in L1 across different cortical areas (data not shown), so the findings likely reflect general principles of L1 organization throughout the neocortex.

    “Comparative histological analysis indicates that the same populations are present in L1 across different cortical areas (data not shown), so our findings likely reflect general principles of L1 organization throughout the neocortex.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Inputs from canopy cells on PCs may be more subject to dendritic filtering and this may contribute at least in part to the apparent difference in synaptic strength recorded at the PC soma.

    “Inputs from canopy cells on PCs may thus be more subject to dendritic filtering and this may contribute at least in part to the apparent difference in synaptic strength recorded at the PC soma.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    A recent comparative analysis of IN single-cell transcriptomes reported broad conservation of molecularly defined IN subtypes across visual and premotor (ALM) cortices.

    “Consistent with this idea, a recent comparative analysis of IN single-cell transcriptomes reported broad conservation of molecularly defined IN subtypes across visual and premotor (ALM) cortices (Tasic et al., 2018).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tasic et al., 2018

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chandelier cells are enriched in L2 and contain a dendritic arborization mostly in L1, often reaching the cortical surface.

    “Chandelier cells are enriched in L2 and contain a dendritic arborization mostly in L1, often reaching the cortical surface (Woodruff et al., 2011;Miyamae et al., 2017).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Woodruff et al., 2011

      Not checked in the free run.

    • cites Miyamae et al., 2017

      Not checked in the free run.

40 of 40

  • The paper relies on this without support.

    The NDNF-ires-Cre driver line specifically labels NDNF-expressing L1 INs.

    “We then generated an NDNF-ires-Cre knock-in driver line (3Ј-UTR) and labeled NDNF-expressing INs via injection of a td-Tomato Cre reporter virus (AAV1.CAG.Flex.tdTomato.WPRE.bGH;Allen Institute 864) in the cortex.”

  • The paper relies on this without support.

    The electrophysiological and morphological properties measured in acute slices reflect those of L1 INs in vivo.

    “We performed whole-cell current clamp recordings in coronal slices of barrel cortex to characterize the intrinsic electrophysiological properties of each L1 population (mice aged P21-P53; mean age Ϯ SEM ϭ P30.3 Ϯ 0.3).”
2 of 2

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 two ends of the PC-3 spectrum resembled layer 1 interneuron populations from a recent barrel cortex study: cells with higher Npy expression matched Ndnf+/Npy+ neurogliaform cells, and the opposite end resembled canopy cells.

    “We noted that each end of the spectrum resembled populations of L1 interneurons described in a recent study in barrel cortex (Schuman et al., 2019): the cells here with higher Npy expression have electrophysiology and morphology consistent with Ndnf+/Npy+ neurogliaform cells, and those at the other end have properties more similar to the “canopy cells” described in that study.”

    From Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells (2020) · cites this paper as Schuman et al., 2019

  • Lamp5-MET-1 cells had action potentials with high upstroke-to-downstroke ratios and neurogliaform-like morphology, and were found mainly in layers 1 and 2/3 but also in deeper layers.

    “Lamp5-MET-1 had APs with high upstroke/downstroke ratios and a neurogliaform-like morphology (Jiang et al., 2013; Jiang et al., 2015; Schuman et al., 2019); these cells were found primarily in L1 and L2/3 but also appeared in deeper cortical layers.”

    From Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells (2020) · cites this paper as Schuman et al., 2019

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Authors
Schuman, B., Machold, R. P., Hashikawa, Y., Fuzik, J., Fishell, G. J., & Rudy, B.
Affiliations
  • New York University (US)
  • Harvard University (US)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2018-11-09
Volume
39
Issue
1
Pages
125-139
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.1613-18.2018
PMC
PMC6325270
OpenAlex
W2900330446
Semantic Scholar
70ba50776b5fd3e4bfed41386e838ac7bd15a885
Cited by
184
References
88
Citations by year
2026: 13 · 2025: 34 · 2024: 25 · 2023: 25 · 2022: 25 · 2021: 24 · 2020: 28 · 2019: 10
FWCI
7.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (UG3MH120096, T32MH096331, R37MH071679)
  • National Institute of Neurological Disorders and Stroke (R01NS107257, P01NS074972, R01NS110079, F31NS106793, R01NS081297)
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
GABAergic interneurons, interneuron subtypes, top-down processing, neuronal morphology, electrophysiological properties, corticocortical connections, sex differences
MeSH terms
Animals, Dendrites, Female, gamma-Aminobutyric Acid, Interneurons, Male, Mice, Transgenic, Pyramidal Cells, Patch-Clamp Techniques, Neocortex, Mice, Electrophysiological Phenomena

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