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Cited by 206Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionVisual perception and processing mechanisms

The DOI matches its Crossref record; 91 of the 95 references it cites were found in a registry or an index; none of the 100 sources its claims cite is checked for support yet.

Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas

Open access
Scala, Federico, Kobak, Dmitry, Shan, Shen, Bernaerts, Yves, Laturnus, Sophie, Cadwell, Cathryn Rene, Hartmanis, Leonard, Froudarakis, Emmanouil, Castro, Jesus Ramon, Tan, Zheng Huan, Papadopoulos, Stelios, Patel, Saumil Surendra, Sandberg, Rickard, Berens, Philipp, Jiang, Xiaolong, Tolias, Andreas Savas·2019·Nature Communications
DOI 10.1038/s41467-019-12058-zPMC PMC6744474

Published version of a preprint

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Abstract

Layer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM + ) non-fast-spiking interneurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM + interneurons were non-Martinotti. These morphologically distinct SOM + interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell type specific circuit motifs, such as the Martinotti/pyramidal and non-Martinotti/stellate pairs, are used across the cortex as building blocks to assemble cortical circuits.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In adult mouse layer 4 (L4), visual cortex (V1) is dominated by pyramidal excitatory neurons and somatostatin-positive (SOM+) Martinotti cells, whereas somatosensory cortex (S1) is dominated by spiny stellate excitatory neurons and SOM+ non-Martinotti cells. These area-specific cell types correspond to different transcriptomic types and differ in local excitatory-to-SOM+ connectivity.

Key findings

  • In V1 L4, 99.1% of recovered excitatory neurons were pyramidal (573/578) and only 0.9% were spiny stellate (5/578); among Viaat-labeled interneurons, SOM+ non-fast-spiking cells were Martinotti cells (20.1%, 47/234), with no non-Martinotti cells found.
  • In S1 L4, 76.6% of recovered spiny neurons were spiny stellate (85/111), and 96.2% of recovered SOM+ neurons were non-Martinotti cells (76/79); both differences from V1 were significant (Fisher’s exact test, p < 0.0001).
  • Patch-seq mapping showed L4 SOM+ cells mostly assigned to Sst Calb2 Pdlim in V1 and Sst Hpse Cbln4 in S1 (S1: 27/29 Hpse; V1: 21/33 Calb2; p < 0.0001), with V1 Hpse cells electrophysiologically intermediate between V1 Calb2 Martinotti cells and S1 non-Martinotti cells.
  • Local excitatory input to SOM+ cells was present in S1 (12.5%, 8/64) but absent in V1 (0%, 0/142; p = 0.0002); SOM+ to excitatory connection probabilities were high in both areas (21.1%, 30/142 in V1; 26.6%, 17/64 in S1), while excitatory-excitatory connectivity was low (1.0%, 7/701 in V1; 2.5%, 3/122 in S1).

Methods

  • Whole-cell patch-clamp recordings with post-hoc morphological recovery in adult mice (V1: n = 129 mice, median age 71 days; 1174 recovered neurons: 578 excitatory, 596 inhibitory), using Cre reporter lines including Viaat-Cre/Ai9, SOM-Cre/Ai9, PV-Cre/Ai9, VIP-Cre/Ai9, and Scnn1a-Cre/Ai9.
  • Simultaneous multi-cell recordings up to eight cells to measure unitary synaptic connections, paired-pulse ratios, and gap-junction coupling, with inter-soma distances generally <150 µm.
  • Patch-seq combined patch-clamp electrophysiology with single-cell RNA sequencing (V1 L4 n = 42, S1 L4 n = 35 after QC, plus L5 cells), mapped to the Tasic et al. transcriptomic atlas; morphological and electrophysiological features were analyzed with regularized logistic regression, t-SNE, and sparse reduced-rank regression.

Limitations

  • Stated: slice electrophysiology can sever neuronal structures, potentially underestimating morphology and connectivity; somatic recordings may fail to detect synapses formed in distal dendrites; low classification accuracy for some morphological pairs (e.g., SBC/HBC) may reflect insufficient sample size.
  • Stated: initial S1 connectivity measurements did not ensure cells were within the same barrel, though a separate intra-barrel experiment was performed.
  • Evident: transcriptomic profiling was limited to SOM+ neurons, not all L4 cell types; morphological classification relied on expert-defined types with some overlapping classes; Patch-seq sample sizes were modest, and the age range was broad (55–330 days in V1 recordings).

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

Integrity signals

Registry

Crossref · 10.1038/s41467-019-12058-z

Cites

91 of 91 references verified0 citation errors · 0 not checkable

Statistics

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Verification

Claims the paper makes

0 of 100 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    All labeled neurons recorded in Scnn1a-Cre/Ai9 mice (n = 5) were morphologically confirmed as pyramidal neurons (100%, 30/30).

    “all labeled neurons recorded in Scnn1a-Cre/Ai9 mice (n = 5), a transgenic mouse line that preferentially labels excitatory neurons in L436,37, were morphologically confirmed as PYRs (100%, 30/30).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [36] Xue, M., Atallah, B. V. & Scanziani, M. Equalizing excitation–inhibition ratios across visual cortical neurons. Nature 511, 596–600 (2014). source
    • cites [37] Harris, J. A. et al. Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation. Front. Neural Circuits 8, 76 (2014). source
  • Findingown data

    The SBC/HBC pair showed only about 0.6 classification accuracy.

    “However, SBC/HBC pair showed only ~0.6 classification accuracy.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Pairwise classification using electrophysiological features showed an average accuracy between fast-spiking types of only 0.67, while the average accuracy across all other pairs was 0.98.

    “the average cross-validated classification accuracy between the FS types was only 0.67, while the average accuracy across all other pairs was 0.98.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Most electrophysiological features exhibited strong differences between cell types.

    “Most features exhibited strong differences between cell types (Supplementary Fig. 5).”
    Quote in the paperSubstantial claim
  • Findingown data

    In S1 L4, 76.6% (85/111) of recovered spiny neurons lacked a clear apical dendrite and were classified as spiny stellate cells, while the remaining 23.4% were pyramidal cells.

    “We found that indeed 76.6% (85/111) of the recovered spiny neurons did not have a clear apical dendrite and were thus classified as spiny stellate cells (Fig. 3b), while the remaining 23.4% were pyramidal cells.”
    Quote in the paperSubstantial claim
  • It may state two separate claims as one. 43
  • The quote only partly states this claim. 3
  • Probably not a substantial claim. 44

  • It may state two separate claims as one.

    Findingown data

    The morphologically distinct SOM+ interneurons in V1 and S1 were differentially integrated into the local circuit, with only S1 neurons receiving local excitatory input.

    “and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Cross-validated pairwise classification of inhibitory cell types using morphological features had an average accuracy of 0.92, with most pairs discriminated almost perfectly.

    “Across all 21 pairs, the average cross-validated classification accuracy was 0.92, with most pairs discriminated almost perfectly (Fig. 2a, left).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    All four PV+ cell types overlapped in one group of electrophysiologically similar fast-spiking neurons, while PYR, NGC, BPC, and MC each had distinct firing patterns.

    “Two-dimensional visualization of this dataset using t-SNE (Fig. 2b) showed that all four PV+ cell types overlapped in one group of electrophysiologically similar FS neurons, while the other four types (PYR, NGC, BPC, and MC) each had distinct firing patterns.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Non-Martinotti cells in S1 L4 differed in firing pattern from Martinotti cells in V1 L4: they had a higher maximal firing rate, a lower action potential width, and a lower membrane time constant.

    “The NMCs also differed in their firing pattern from MCs recorded in V1: they had a higher maximal firing rate, a lower AP width, and a lower membrane time constant (Fig. 4a, Supplementary Fig. 5).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    All SOM+ non-fast-spiking interneurons in V1 L4 were Martinotti cells, and Martinotti cells were the only SOM+ cell type.

    “all somatostatin-positive (SOM+) non-fast-spiking interneurons were Martinotti cells”
    • Also stated in: § Morphological cell types in L4 of adult mouse visual cortex · plain
      “Martinotti cells (MCs; 20.1%, 47/234), characterized by an ascending axon that projected to L1 and by the large membrane time constant, were the only SOM+ cell type.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    VIP+ neurons in V1 L4 were represented by bipolar cells (12.4%, 29/234) with a small soma, dendrites extending to L1 and L5, an axon projecting mostly downward to L5, and an irregular firing pattern.

    “VIP+ neurons were represented by the bipolar cells (BPCs; 12.4%, 29/234) with a small soma, dendrites extending to L1 and L5, an axon projecting mostly downward to L5, and an irregular firing pattern.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    Among interneurons labeled in Viaat-Cre, large basket cells were most common (37.6%, 88/234), followed by small basket cells (9.4%, 22/234), double-bouquet basket cells (5.6%, 13/234), and horizontally elongated basket cells (3.4%, 8/234).

    “the most common were large basket cells (LBCs; 37.6% among the interneurons labeled in Viaat-Cre, 88/234), followed by small basket cells (SBCs; 9.4%, 22/234), double-bouquet basket cells (DBCs; 5.6%, 13/234), and horizontally elongated basket cells (HBCs; 3.4%, 8/234).”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: All four PV+ fast-spiking cell types were basket cells with different axonal morphologies.

  • It may state two separate claims as one.

    Findingown data

    Four distinct types of PV+ fast-spiking cells were found in V1 L4, with narrow action potential width, high maximal firing rate, and thick axons.

    “We found four distinct types of PV+, fast-spiking (FS) cells with narrow AP width, high maximal firing rate, and thick axons.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    In V1 L4, Martinotti cells did not show the heterogeneity reported for L5 Martinotti cells; none showed rebound firing after stimulation offset.

    “Previous literature suggested that Martinotti cells in L5 form two groups with different morphology and/or electrophysiology29,42, but we did not observe such heterogeneity in L4: in particular, none of the MCs showed a rebound firing after stimulation offset42.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source
    • cites [42] Nigro, M. J., Hashikawa-Yamasaki, Y. & Rudy, B. Diversity and connectivity of layer 5 somatostatin-expressing interneurons in the mouse barrel cortex. J. Neurosci. 38, 1622–1633 (2018). source

  • It may state two separate claims as one.

    Findingown data

    Most L4 SOM+ cells (81%, 62/77) were assigned to Sst Calb2 Pdlim and Sst Hpse Cbln4 transcriptomic types, with S1 cells falling almost exclusively into the Hpse type (27/29) and V1 cells preferentially into the Calb2 type (21/33) (p < 0.0001).

    “Most L4 cells (81%, 62/77) were assigned to Sst Calb2 Pdlim and Sst Hpse Cbln4 transcriptomic types (Fig. 4b, e), with S1 cells falling almost exclusively into the Hpse type (27/29) and V1 cells falling preferentially into the Calb2 type (21/33) (p < 0.0001, Fisher’s exact test).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    In S1 L4, almost all recovered SOM+ neurons (96.2%, 76/79) had non-Martinotti cell morphology; only two cells showed Martinotti cell morphology (2.5%, 2/79) and one had a large-basket-cell-like thick axon with fast-spiking firing (1.3%, 1/79) (Fisher's exact test p < 0.0001; 76/79 vs. 0/61).

    “Indeed, we found that in S1, almost all L4 SOM+ neurons we recovered (96.2%, 76/79, from n = 19 SOM-Cre/Ai9 mice) had NMC morphology characterized by a thin, highly ramifying axon mostly residing within L4 (Fig. 3b). Only two cells showed an ascending axon projecting to L1 typical of MCs (2.5%, 2/79) and one was characterized by a thick axon branching similarly to LBC with a FS firing pattern (1.3”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    A small fraction of SOM+ neurons in V1 L4 exhibited a fast-spiking firing pattern and their morphological features matched large basket cells (8.2%, 5/61).

    “A small fraction of SOM+ neurons exhibited an FS firing pattern and their morphological features matched those of LBCs (8.2%, 5/61; Supplementary Fig. 2), in agreement with the previous reports that due to potential off-target recombination, ~5–20% of neurons labeled in SOM-Cre line are FS29,43,44 and PV+/SOM− at the protein level43.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source
    • cites [43] Hu, H., Cavendish, J. Z. & Agmon, A. Not all that glitters is gold: off-target recombination in the somatostatin–IRES-Cre mouse line labels a subset of fast-spiking interneurons. Front. Neural Circuits 7, 195 (2013). source
    • cites [44] Reimer, J. et al. Pupil fluctuations track fast switching of cortical states during quiet wakefulness. Neuron 84, 355–362 (2014). source
    • The authors state this as an assumption: All four PV+ fast-spiking cell types were basket cells with different axonal morphologies.

  • It may state two separate claims as one.

    Findingown data

    V1 L4 pyramidal neurons exhibited large action potential width, high action potential amplitude, and shallow afterhyperpolarization, which discriminated them from GABAergic interneurons.

    “PYRs exhibited large action potential (AP) width, high AP amplitude, and shallow afterhyperpolarization (AHP), which clearly discriminated them from GABAergic interneurons”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    Nearly all excitatory neurons in V1 L4 were pyramidal; 573 of 578 (99.1%) excitatory cells were pyramidal neurons.

    “Nearly all excitatory neurons were pyramidal”
    • Also stated in: § Morphological cell types in L4 of adult mouse visual cortex · plain
      “Out of the 578 excitatory cells, 573 (99.1%) were pyramidal neurons (PYR), characterized by apical dendrites extending into layer 1 (L1)”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    t-SNE visualization indicated that SBC/HBC types were partially overlapping, as well as LBC/DBC.

    “Visualization of this dataset with t-SNE (Fig. 2a, right) indicated that SBC/HBC types were partially overlapping, as well as LBC/DBC.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingreasoning

    In S1, axons of L4 NMCs were more localized, matching the more compact dendritic structure of spiny stellate cells.

    “In S1, by contrast, axons of L4 NMCs were more localized, matching the more compact dendritic structure of spiny stellate cells.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    L5 SOM+ cells sequenced in both areas mostly mapped to a different set of transcriptomic types than L4 SOM+ cells, with no apparent differences between S1 and V1 in transcriptomic cell types.

    “The L5 SOM+ cells that we sequenced in both areas mostly mapped to a different set of transcriptomic types than the L4 SOM+ cells, but there were no apparent differences between S1 and V1 in terms of transcriptomic cell types (Fig. 4b).”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    Large basket cells in V1 L4 followed the same connectivity rules as previously found in other layers: PYRs connected to LBCs with probability 12.5% (38/303), MCs inhibited LBCs with probability 32.6% (15/46), and LBCs inhibited each other (36.7%, 75/204), MCs (13.0%, 6/46) and PYRs (25.7%, 78/303).

    “We found that LBCs followed the same connectivity rules as previously found in other layers29,49. PYRs connected to LBCs with probability 12.5% (38/303), MCs inhibited LBCs with probability 32.6% (15/46), and LBCs inhibited each other (36.7%, 75/204), MCs (13.0%, 6/46) and PYRs (25.7%, 78/303).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source
    • cites [49] Pfeffer, C. K., Xue, M., He, M., Huang, Z. J. & Scanziani, M. Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons. Nat. Neurosci. 16, 1068–1076 (2013). source
    • The authors state this as an assumption: All four PV+ fast-spiking cell types were basket cells with different axonal morphologies.

  • It may state two separate claims as one.

    Findingown data

    The connection probability between pyramidal neurons in V1 L4 was very low, consistent with previous work in other layers in adult animals but in contrast to findings in young and juvenile rodents.

    “Notably, the connection probability between PYRs in V1 L4 was very low, consistent with our previous work in other layers in adult animals29, but in contrast to the findings in young and juvenile rodents51,52.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source
    • cites [51] Markram, H., Lübke, J., Frotscher, M., Roth, A. & Sakmann, B. Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. J. Physiol. 500, 409–440 (1997). source
    • cites [52] Song, S., Sjöström, P. J., Reigl, M., Nelson, S. & Chklovskii, D. B. Correction: highly nonrandom features of synaptic connectivity in local cortical circuits. PLoS Biol. 3, e350 (2005). source

  • It may state two separate claims as one.

    Findingown data

    In V1 L4, there were no connections from local excitatory neurons to Martinotti cells (0%, 0/142), differing from S1 (p = 0.0002).

    “In contrast, we did not find any connections (0%, 0/142) from local excitatory neurons to MCs in V1 (p = 0.0002, Fisher’s exact text).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    The measured intra-barrel connection probability (5.2%, 5/104) was not significantly different from the value reported above (2.5%, 3/122) (p = 0.48, Fisher's exact test).

    “but not significantly different from it (p = 0.48, Fisher’s exact test)”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    These cells (MCs from V1 mapping to Sst Hpse Cbln4) show an electrophysiological profile intermediate between MCs and NMCs, but morphologically correspond to MCs.

    “These cells show an electrophysiological profile intermediate between MCs and NMCs, but morphologically correspond to MCs based on our data.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Large basket cells were electrically coupled to each other with probability 27.5% (28/102) but were never electrically coupled to Martinotti cells (0/23).

    “We also found that LBCs were electrically coupled to each other with probability 27.5% (28/102) but were never electrically coupled to MCs (0/23), in agreement with previous findings that gap junctions exist between inhibitory cells of the same type50.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Galarreta, M. & Hestrin, S. Electrical synapses between GABA-releasing interneurons. Nat. Rev. Neurosci. 2, 425–433 (2001). source
    • The authors state this as an assumption: All four PV+ fast-spiking cell types were basket cells with different axonal morphologies.

  • It may state two separate claims as one.

    Findingown data

    Both MCs in V1 and NMCs in S1 projected to the excitatory population in L4.

    “and projected to excitatory population in L4.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data

    Across genes, there was a clear inverse relationship between mean non-zero expression (μ) and probability of near-zero expression (τ), roughly following the exponential law τ ≈ exp(−1.5⋅μ + a) for some horizontal offset a.

    “Across genes, there was a clear inverse relationship between μ and τ, that roughly followed exponential law τ ≈ exp(−1.5⋅μ + a) for some horizontal offset a.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data

    All the remaining 110 cells mapped to the Sst types.

    “All the remaining n = 110 cells mapped to the Sst types.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingcitation

    Tissue shrinkage due to fixation and staining was about 10-20%, consistent with previous studies.

    “Tissue shrinkage due to the fixation and staining procedures was about 10–20%, consistent with previous studies29,51.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source
    • cites [51] Markram, H., Lübke, J., Frotscher, M., Roth, A. & Sakmann, B. Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. J. Physiol. 500, 409–440 (1997). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data

    The afterdepolarization (ADP) feature was equal to zero for most neurons.

    “ADP because it was equal to zero for most neurons”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingcitation

    The remaining 114 cells were mapped to the full set of 133 transcriptomic types identified in Tasic et al.

    “The remaining n = 114 cells were mapped to the full set of 133 transcriptomic types identified in Tasic et al.25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tasic et al.25 Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source

  • The quote only partly states this claim.

    Findingown data

    We found differences in the connections from excitatory neurons to SOM+ interneurons between V1 and S1.

    “Furthermore, we found differences in the connections from excitatory neurons to SOM+ interneurons”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    We identified seven morphological types of interneurons but only four electrophysiological types in our V1 L4 dataset.

    “In our V1 L4 dataset, we identified seven morphological types of interneurons but only four electrophysiological types (Fig. 2)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data

    The first action potential latency feature had high outliers among the fast-spiking (FS) types.

    “latency because it had high outliers among the FS types”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data

    The total number of sequenced cells was 118.

    “The total number of sequenced cells was n = 118.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    Somatostatin-positive (SOM+) interneurons form a single morphological population called non-Martinotti cells, with axons mainly targeting L4, in contrast to typical Martinotti cells that target L1.

    “Several recent studies revealed that the somatostatin-positive (SOM+) interneurons form a single morphological population that has been called non-Martinotti cells13 since their axons mainly target L414,15, in contrast to typical Martinotti cells, which target L1.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [13] Yavorska, I. & Wehr, M. Somatostatin-expressing inhibitory interneurons in cortical circuits. Front. Neural Circuits 10, 76 (2016). source
    • cites [14] Ma, Y., Hu, H., Berrebi, A. S., Mathers, P. H. & Agmon, A. Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice. J. Neurosci. 26, 5069–5082 (2006). source
    • cites [15] Xu, H., Jeong, H.-Y., Tremblay, R. & Rudy, B. Neocortical somatostatin-expressing GABAergic interneurons disinhibit the thalamorecipient layer 4. Neuron 77, 155–167 (2013). source

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation

    Layer 4 (L4) of mammalian neocortex is the main direct target of sensory inputs from the thalamus and acts as the first level of cortical processing for sensory signals.

    “In this stereotypical architecture, layer 4 (L4) is the main direct target of sensory inputs coming from the thalamus, thus acting as the first level of cortical processing for sensory signals1.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Harris, K. D. & Shepherd, G. M. G. The neocortical circuit: themes and variations. Nat. Neurosci. 18, 170–181 (2015). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    Inhibitory interneurons in L4 are highly diverse in genetic markers, morphologies and electrophysiological properties.

    “In contrast, inhibitory interneurons are highly diverse in terms of their genetic markers, morphologies and electrophysiological properties10.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Tremblay, R., Lee, S. & Rudy, B. GABAergic interneurons in the neocortex: from cellular properties to circuits. Neuron 91, 260–292 (2016). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    Previous studies reported three types of fast-spiking (FS), parvalbumin-positive (PV+) interneurons and five types of non-FS interneurons, all with distinct morphologies.

    “Previous studies have reported three types of fast-spiking (FS), parvalbumin-positive (PV+) interneurons11 and five types of non-FS interneurons12, all of which have distinct morphologies.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] Koelbl, C., Helmstaedter, M., Lübke, J. & Feldmeyer, D. A Barrel-related interneuron in layer 4 of rat somatosensory cortex with a high intrabarrel connectivity. Cereb. Cortex 25, 713–725 (2013). source
    • cites [12] Emmenegger, V., Qi, G., Wang, H. & Feldmeyer, D. Morphological and functional characterization of non-fast-spiking GABAergic interneurons in layer 4 microcircuitry of rat barrel cortex. Cereb. Cortex 28, 1439–1457 (2018). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    PV+ FS interneurons receive strong thalamic inputs while SOM+ non-FS interneurons receive weaker thalamic inputs.

    “For example, PV+ FS interneurons receive strong thalamic inputs16–20 while SOM+ non-FS interneurons receive weaker thalamic inputs21,22.”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [16] Cruikshank, S. J., Lewis, T. J. & Connors, B. W. Synaptic basis for intense thalamocortical activation of feedforward inhibitory cells in neocortex. Nat. Neurosci. 10, 462–468 (2007). source
    • cites [17] Beierlein, M., Gibson, J. R. & Connors, B. W. Two dynamically distinct inhibitory networks in layer 4 of the neocortex. J. Neurophysiol. 90, 2987–3000 (2003). source
    • cites [18] Higley, M. J. & Contreras, D. Balanced excitation and inhibition determine spike timing during frequency adaptation. J. Neurosci. 26, 448–457 (2006). source
    • cites [19] Gabernet, L., Jadhav, S. P., Feldman, D. E., Carandini, M. & Scanziani, M. Somatosensory integration controlled by dynamic thalamocortical feed-forward inhibition. Neuron 48, 315–327 (2005). source
    • cites [20] Kloc, M. & Maffei, A. Target-specific properties of thalamocortical synapses onto layer 4 of mouse primary visual cortex. J. Neurosci. 34, 15455–15465 (2014). source
    • cites [21] Cruikshank, S. J., Urabe, H., Nurmikko, A. V. & Connors, B. W. Pathway-specific feedforward circuits between thalamus and neocortex revealed by selective optical stimulation of axons. Neuron 65, 230–245 (2010). source
    • cites [22] Ji, X.-Y. et al. Thalamocortical innervation pattern in mouse auditory and visual cortex: laminar and cell-type specificity. Cereb. Cortex 26, 2612–2625 (2016). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Interpretationown data

    Three cells with fast-spiking firing pattern mapped to Pvalb Reln Itm2a transcriptomic type, likely corresponding to basket cells labeled in SOM-Cre; they did not express SOM, suggesting transient expression during development.

    “Three cells (excluded from the cell counts given above and from further analysis) had fast-spiking firing pattern and mapped to Pvalb Reln Itm2a transcriptomic type, likely corresponding to the basket cells that we found labeled in the SOM-Cre line (Fig. 3). These three cells did not express SOM (zero read count), suggesting that they could have transiently expressed it during development, as hyp”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Hu, H., Cavendish, J. Z. & Agmon, A. Not all that glitters is gold: off-target recombination in the somatostatin–IRES-Cre mouse line labels a subset of fast-spiking interneurons. Front. Neural Circuits 7, 195 (2013). source

  • It may state two separate claims as one.

    Interpretationown data

    No labeled neurogliaform cells were encountered in PV-Cre, SST-Cre, or VIP-Cre lines, suggesting they belonged to the Lamp5 transcriptomic family.

    “We did not encounter any labeled NGCs in PV-Cre, SST-Cre, or VIP-Cre lines, suggesting that they belonged to the Lamp5 transcriptomic family25.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source

  • It may state two separate claims as one.

    Interpretationown data

    The quality of mapping Patch-seq cells to the transcriptomic dataset was equally good for V1 and S1 cells, suggesting the V1 + ALM dataset is a reasonable reference for S1 interneurons.

    “The quality of the mapping was equally good for V1 and S1 cells (Supplementary Fig. 7), suggesting that the V1 + ALM dataset is a reasonable reference for S1 interneurons, in agreement with the idea that inhibitory transcriptomic cell types are shared across cortical regions25,26.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source
    • cites [26] Nowakowski, T. J. et al. Regulation of cell-type-specific transcriptomes by microRNA networks during human brain development. Nat. Neurosci. 21, 1784–1792 (2018). source

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation

    Recent large-scale transcriptomic studies showed that most interneuron types are shared between cortical areas while excitatory types are predominantly area-specific.

    “Recent large-scale studies of transcriptomic cell types in mouse and human cortex showed that most interneuron types are shared between cortical areas while the excitatory types are predominantly area-specific25,26.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source
    • cites [26] Nowakowski, T. J. et al. Regulation of cell-type-specific transcriptomes by microRNA networks during human brain development. Nat. Neurosci. 21, 1784–1792 (2018). source

  • It may state two separate claims as one.

    Interpretationown data

    Most morphological classes can be very well discriminated, but some may be partially overlapping.

    “Overall, this analysis suggests that while most morphological classes can be very well discriminated, some may be partially overlapping.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationcitation

    Sst Calb2 Pdlim is a Martinotti cell type and Sst Hpse Cbln4 is a non-Martinotti cell type.

    “This suggests that Sst Calb2 Pdlim is a MC type, in agreement with the conclusions of Tasic et al.25 based on the data from Paul et al.46, and that Sst Hpse Cbln4 is a NMC type, in agreement with Naka et al.47.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [25] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source
    • cites [46] Paul, A. et al. Transcriptional architecture of synaptic communication delineates GABAergic neuron identity. Cell 171, 522–539.e20 (2017). source
    • cites [47] Naka, A. et al. Complementary networks of cortical somatostatin interneurons enforce layer specific control. eLife 8, e43696 (2019). source

  • It may state two separate claims as one.

    Premisecitation

    Recent evidence indicates that most, if not all, L4 SOM+ cells in mouse S1 have axons mostly localized within L4, in contrast to typical Martinotti cells, and are called non-Martinotti cells.

    “Recent evidence indicates that most, if not all, L4 SOM+ cells in mouse S1 have axons mostly localized within L4, in stark contrast to typical MCs15, and have been called non-Martinotti cells (NMCs)13.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [15] Xu, H., Jeong, H.-Y., Tremblay, R. & Rudy, B. Neocortical somatostatin-expressing GABAergic interneurons disinhibit the thalamorecipient layer 4. Neuron 77, 155–167 (2013). source
    • cites [13] Yavorska, I. & Wehr, M. Somatostatin-expressing inhibitory interneurons in cortical circuits. Front. Neural Circuits 10, 76 (2016). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    Gap junctions exist between inhibitory cells of the same type.

    “in agreement with previous findings that gap junctions exist between inhibitory cells of the same type50.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Galarreta, M. & Hestrin, S. Electrical synapses between GABA-releasing interneurons. Nat. Rev. Neurosci. 2, 425–433 (2001). source

  • Probably not a substantial claim.

    Premisecitation

    In S1 L4, cells preferentially make intra-barrel connections.

    “it is known that cells in S1 L4 preferentially make intra-barrel connections3,4.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] Feldmeyer, D., Egger, V., Lübke, J. & Sakmann, B. Reliable synaptic connections between pairs of excitatory layer 4 neurones within a single ‘barrel’ of developing rat somatosensory cortex. J. Physiol. 521, 169–190 (1999). source
    • cites [4] Petersen, C. C. H. & Sakmann, B. The excitatory neuronal network of rat layer 4 barrel cortex. J. Neurosci. 20, 7579–7586 (2000). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    Martinotti cells in L2/3 and L5 of adult mouse V1 receive strong facilitating synaptic inputs from local pyramidal neurons in the same layers.

    “This was also in stark contrast to MCs in L2/3 and L5 of adult mouse V1, which receive strong facilitating synaptic inputs from local PYRs in the same layers29”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    A recent study found 6.3% (20/315) connection probability in V1 L4 of P46 mice.

    “This is in agreement with a recent study that found 6.3% (20/315) connection probability in V1 L4 of P46 mice53.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Seeman, S. C. et al. Sparse recurrent excitatory connectivity in the microcircuit of the adult mouse and human cortex. Elife 7, e37349 (2018). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    All these large basket cell connection patterns have also been reported in S1 L4 of young mice.

    “All of these connection patterns have also been reported in S1 L4 of young mice24.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Ma, Y., Hu, H. & Agmon, A. Short-term plasticity of unitary inhibitory-to-inhibitory synapses depends on the presynaptic interneuron subtype. J. Neurosci. 32, 983–988 (2012). source

  • It may state two separate claims as one.

    Premisecitation

    All non-fast-spiking SOM+ cells in V1 L5 and the majority of SOM+ cells in S1 L5 are known to be Martinotti cells.

    “Morphologically, all non-fast-spiking SOM+ cells in V1 L529,47 and the majority of SOM+ cells in S1 L522,29,42,47 are known to be MCs.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source
    • cites [47] Naka, A. et al. Complementary networks of cortical somatostatin interneurons enforce layer specific control. eLife 8, e43696 (2019). source
    • cites [22] Ji, X.-Y. et al. Thalamocortical innervation pattern in mouse auditory and visual cortex: laminar and cell-type specificity. Cereb. Cortex 26, 2612–2625 (2016). source
    • cites [42] Nigro, M. J., Hashikawa-Yamasaki, Y. & Rudy, B. Diversity and connectivity of layer 5 somatostatin-expressing interneurons in the mouse barrel cortex. J. Neurosci. 38, 1622–1633 (2018). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    The excitatory identity controls the survival and wiring of local interneurons.

    “This observation is in line with previous findings that the excitatory identity controls the survival and wiring of local interneurons60,61.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [60] Lodato, S. et al. Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex. Neuron 69, 763–779 (2011). source
    • cites [61] Wong, F. K. et al. Pyramidal cell regulation of interneuron survival sculpts cortical networks. Nature 557, 668–673 (2018). source

  • Probably not a substantial claim.

    Premisecitation

    The majority of transcriptomic inhibitory types are shared between two very different cortical areas (V1 and ALM).

    “Tasic et al.25 showed that the majority of transcriptomic inhibitory types are shared between two very different cortical areas (V1 and ALM).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductreasoning

    Neuronal structures can be severed due to slicing, introducing a potential underestimation of neuronal morphology and connectivity.

    “Importantly, neuronal structures can be severed (a limitation of all slice electrophysiology experiments) due to the slicing procedure, introducing a potential underestimation of neuronal morphology and connectivity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductown data

    Pairwise classification used nested cross-validation with logistic regression regularized with elastic net.

    “For pairwise classification, we used exactly the same procedure as described above for pairwise classification using the reconstructed morphologies (nested cross-validation with logistic regression regularized with elastic net).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    Investigators were blinded to cell type of Patch-seq samples during library construction and sequencing.

    “Investigators were blinded to cell type of Patch-seq samples during library construction and sequencing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    Four cells were excluded because the sum of counts across all genes was below 1500.

    “Four cells were excluded because the sum of counts across all genes was below 1500”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    Naka et al. showed that L4 excitatory neurons connect to NMCs in L5 but not to MCs in L5.

    “Within S1, Naka et al.47 showed that L4 excitatory neurons connect to NMCs in L5 but not to MCs in L5”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Naka, A. et al. Complementary networks of cortical somatostatin interneurons enforce layer specific control. eLife 8, e43696 (2019). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    This potential underestimation did not seem to strongly affect studies of local circuits in the past.

    “However, this did not seem to strongly affect the studies of local circuits in the past29,78.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source
    • cites [78] Qi, G., Radnikow, G. & Feldmeyer, D. Electrophysiological and morphological characterization of neuronal microcircuits in acute brain slices using paired patch-clamp recordings. J. Vis. Exp. 95, e52358 (2015). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductown data

    Eight cells did not have good electrophysiological recordings and were excluded from all downstream analyses that required electrophysiological data, leaving 102 cells.

    “Among those, eight cells did not have good electrophysiological recordings (the recordings were either lost or were of bad quality) and were excluded from all downstream analyses that required electrophysiological data (leaving n = 102 cells).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Interpretationown data

    L4 MCs in V1 behave differently from SOM+ MCs in other layers.

    “However, our results suggest that L4 MCs in V1 behave differently.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. It may state two separate claims as one.

    Study design and conductown data

    Neurons were assigned to L4 based on neocortical layer boundaries and small somata, and layer identity was confirmed by visualization after staining.

    “Neurons were assigned to L4 based on the neocortical layer boundaries and the small somata that characterize this layer, which were clearly visible in the micrograph under the bright-field microscope. The layer identity of each neuron was also confirmed by the visualization of their position after the staining.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    Animal preparation procedures were performed according to protocols approved by the IACUC of Baylor College of Medicine.

    “Animal preparation procedures for animals maintenance and surgeries were performed according to protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Baylor College of Medicine.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    Ten-fold cross-validation was used to select the values of alpha and lambda regularization parameters that would maximize the predicted R-squared.

    “We used 10-fold cross-validation to select the values of alpha and lambda regularization parameters that would maximize the predicted R-squared.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    Our recordings were done at the soma and could have failed to detect synaptic connections formed in the distal dendrites.

    “One possible caveat here is that our recordings were done at the soma and could have failed to detect synaptic connections formed in the distal dendrites.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Study design and conductown data

    To make sure that identified connections were monosynaptic, we recovered the morphology of presynaptic neurons and made sure that morphology and electrophysiology matched the nature of connections (EPSP vs. IPSP).

    “To make sure that the identified connections were monosynaptic, we recovered the morphology of the presynaptic neurons and made sure that the morphology and electrophysiology of the presynaptic neuron for each connection (i.e., pyramidal neurons vs. interneurons) matched the nature of connections (i.e., EPSP vs. IPSP).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. It may state two separate claims as one.

    Study design and conductcitation

    Because synaptic connectivity strongly depends on inter-soma distance, we took special care to record from groups of neurons with inter-soma distances less than 150 μm.

    “Because the synaptic connectivity strongly depends on the inter-soma distance29, we took special care to record from groups of neurons with inter-soma distances less than 150 µm.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    Outer-loop performance was assessed via test-set accuracy.

    “Outer-loop performance was assessed via test-set accuracy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    Three cells were excluded because they mapped to the Pvalb Reln Itm2a type and were fast-spiking.

    “three cells were excluded because they mapped to Pvalb Reln Itm2a type (and were fast-spiking)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    The analysis shown in Fig. 4e used 102 Patch-seq cells with high-quality electrophysiological recordings.

    “For the analysis shown in Fig. 4e, we selected 1000 most variable genes as described above, using n = 102 Patch-seq cells with high-quality electrophysiological recordings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    One cell was excluded because it mapped to one of the excitatory types.

    “One cell was excluded because it mapped to one of the excitatory types”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    Gowens et al. identified twice as many morphological types (m-types) as electrophysiological ones (e-types) in a parallel work based on unsupervised clustering.

    “This is in qualitative agreement with the findings of Gowens et al.76, who, in a parallel work based on unsupervised clustering, identified twice as many morphological types (m-types) as electrophysiological ones (e-types).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Gouwens, N. W. et al. Classification of electrophysiological and morphological neuron types in the mouse visual cortex. Nat. Neurosci. 22, 1182–1195 (2019). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    The shrinkage was not compensated for the morphology visualization and analysis.

    “The shrinkage was not compensated for the morphology visualization and analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper may give no reason why it holds.

    Study design and conductnone given

    The problem of failing to detect distal connections would not be more severe in adult animals compared to young ones (P15-20).

    “However, we see no reason to believe that this problem would be more severe in adult animals compared to the young ones (P15–20)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    In V1, L4 MCs receive weak inputs from the thalamus compared to other interneuron types.

    “previous studies have shown that in V1, L4 MCs also receive weak inputs from the thalamus compared to other interneuron types21,22.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Cruikshank, S. J., Urabe, H., Nurmikko, A. V. & Connors, B. W. Pathway-specific feedforward circuits between thalamus and neocortex revealed by selective optical stimulation of axons. Neuron 65, 230–245 (2010). source
    • cites [22] Ji, X.-Y. et al. Thalamocortical innervation pattern in mouse auditory and visual cortex: laminar and cell-type specificity. Cereb. Cortex 26, 2612–2625 (2016). source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    Special care was taken to select only slices that had a cutting plane parallel to the apical dendrites to ensure preservation of both axonal and dendritic arborization structures.

    “special care was taken to select only slices that had a cutting plane parallel to the apical dendrites to ensure preservation of both axonal and dendritic arborization structures.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Interpretationreasoning

    The difference in the morphology of SOM+ neurons between V1 and S1 might be a result of the difference in dendritic arborization of the targeted excitatory neurons.

    “We suggest that the difference in the morphology of SOM+ neurons between these two cortical areas might be a result of the difference in dendritic arborization of the targeted excitatory neurons.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    SOM+ MCs in other layers receive facilitating excitatory inputs from local principal neurons in both S1 and V1.

    “SOM+ MCs in other layers are known to receive facilitating excitatory inputs from local principal neurons in both S162,63 and V129,64.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [62] Kapfer, C., Glickfeld, L. L., Atallah, B. V. & Scanziani, M. Supralinear increase of recurrent inhibition during sparse activity in the somatosensory cortex. Nat. Neurosci. 10, 743–753 (2007). source
    • cites [63] Silberberg, G. & Markram, H. Disynaptic inhibition between neocortical pyramidal cells mediated by Martinotti cells. Neuron 53, 735–746 (2007). source
    • cites [29] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462–aac9462 (2015). source
    • cites [64] Adesnik, H., Bruns, W., Taniguchi, H., Huang, Z. J. & Scanziani, M. A neural circuit for spatial summation in visual cortex. Nature 490, 226–231 (2012). source

  • Probably not a substantial claim. It may state two separate claims as one.

    Study design and conductnone given

    We used nested cross-validation to choose the optimal value of the regularization parameter lambda and to obtain an unbiased estimate of the performance.

    “We used nested cross-validation to choose the optimal value of the regularization parameter lambda and to obtain an unbiased estimate of the performance.”
    Quote in the paperSubstantial claim
79 of 79

  • The authors state this as an assumption.

    All four PV+ fast-spiking cell types were basket cells with different axonal morphologies.

    “None of them had chandelier-like axonal structures, so we assumed that all four types were basket cells with different axonal morphologies10”

  • The paper relies on this without support.

    There has been no systematic comparison of anatomical and electrophysiological properties as well as connectivity profiles between L4 of different cortical areas.

    “However, there has been no systematic comparisons of anatomical and electrophysiological properties as well as connectivity profiles between L4 of different cortical areas, leaving an open question about the similarity in their cellular components and circuitry.”
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 Sst Pvalb Calb2 type, which is transcriptomically in between the Sst and Pvalb subclasses, was also in between these subclasses in terms of its morpho-electric phenotype.

    “Another finding was that the Sst Pvalb Calb2 type, which is transcriptomically in between the Sst and Pvalb subclasses, was also in between these subclasses in terms of its morpho-electric phenotype28.”

    From Phenotypic variation of transcriptomic cell types in mouse motor cortex (2021) · cites this paper as [28]

  • Tissue shrinkage due to the fixation and staining procedures was about 10-20%.

    “Consistently with previous studies, tissue shrinkage due to the fixation and staining procedures was about 10–20%5,28,49.”

    From Phenotypic variation of transcriptomic cell types in mouse motor cortex (2021) · cites this paper as [28]

  • Recent evidence suggests that different morphological phenotypes correspond to different synaptic connectivity profiles.

    “Recent evidence also suggests that different morphological phenotypes correspond to differential synaptic connectivity profiles (Nigro et al., 2018; Naka et al., 2019; Scala et al., 2019).”

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

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Within-barrel connection probability does not match its count

    Minor

    Five connections out of 104 tested correspond to 4.8%, not the reported 5.2%.

    Reported 5.2 · recomputed 4.807692

1 of 1

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Metadata

Authors
Scala, F., Kobak, D., Shan, S., Bernaerts, Y., Laturnus, S., Cadwell, C. R., Hartmanis, L., Froudarakis, E., Castro, J. R., Tan, Z. H., Papadopoulos, S., Patel, S. S., Sandberg, R., Berens, P., Jiang, X., & Tolias, A. S.
Affiliations
  • Baylor College of Medicine (US)
  • University of Tübingen (DE)
  • Karolinska Institutet (SE)
Corresponding author
  • Jiang, Xiaolong
  • Tolias, Andreas Savas
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-09-13
Volume
10
Issue
1
Pages
4174-4174
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-12058-z
PMC
PMC6744474
OpenAlex
W2973144132
Semantic Scholar
37f874c21f68b57cf82e9d67a01769a259bbe382
Cited by
193
References
95
Citations by year
2026: 16 · 2025: 37 · 2024: 27 · 2023: 42 · 2022: 31 · 2021: 20 · 2020: 13 · 2019: 6
FWCI
8.36
Type
journal article
Language
en
Update notices
correction (2019-11-04)
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Science Foundation (1707359)
  • Deutsche Forschungsgemeinschaft (EXC2064, (BE5601/4-1, 276693517, 390727645, SFB1233)
  • Bundesministerium für Bildung und Forschung (FKZ 01GQ1601, 01GQ1601)
  • National Institutes of Health
  • Intelligence Advanced Research Projects Activity (D16PC00003)
  • Interior Business Center
  • National Institute of Mental Health (R01MH109556, R01MH120404, MH109556, R01MH122169, U19MH114830)
  • National Institute of Neurological Disorders and Stroke
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 › Cognitive Neuroscience › Visual perception and processing mechanisms
Keywords
layer 4, neocortex, mouse visual cortex, somatosensory cortex, cortical cell types, Martinotti cells, somatostatin interneurons, pyramidal neurons, stellate neurons, inhibitory interneurons, excitatory-inhibitory connectivity
MeSH terms
Animals, Electrophysiology, Female, Interneurons, Male, Neurons, Somatosensory Cortex, Somatostatin, Neocortex, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Statistics and arithmetic are recomputed, not judged.

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

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

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