The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index; 4 of the 53 sources its claims cite were checked for support.
Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type
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Abstract
We describe convergent evidence from transcriptomics, morphology, and physiology for a specialized GABAergic neuron subtype in human cortex. Using unbiased single-nucleus RNA sequencing, we identify ten GABAergic interneuron subtypes with combinatorial gene signatures in human cortical layer 1 and characterize a group of human interneurons with anatomical features never described in rodents, having large ‘rosehip’-like axonal boutons and compact arborization. These rosehip cells show an immunohistochemical profile (GAD1+CCK+, CNR1–SST–CALB2–PVALB–) matching a single transcriptomically defined cell type whose specific molecular marker signature is not seen in mouse cortex. Rosehip cells in layer 1 make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons, and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons. The authors use single-nucleus RNA-seq to identify 10 GABAergic interneuron subtypes in human cortex layer 1. Molecular, morphological, and physiological evidence points to an emerging human cell type, the rosehip cell, not found in other species.
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“Rosehip cells in layer 1 make homotypic gap junctions”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
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“Somata and dendrites of RCs were confined to layer 1 with only distal dendrites occasionally penetrating layer 2.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“predominantly target apical dendritic shafts of layer 3 pyramidal neurons”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
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“Proximal dendrites and somata of RCs were decorated with stub-like spines.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“Unbiased recordings of layer 1 cell types yielded a set of interneurons with complete axo-somato-dendritic recovery (n=76).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“The layer 1 MTG transcriptomic clusters expressed either SST (i1,i2), VIP (i6, i9, i10), or neither marker”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
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“inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
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“whose specific molecular marker signature is not seen in mouse cortex”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
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“Using unbiased single nucleus RNA sequencing, we identify ten GABAergic interneuron subtypes with combinatorial gene signatures in human cortical layer 1”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
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“Furthermore, each cluster showed highly selective expression of known and previously uncharacterized individual marker genes.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
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“These clusters in layer 1 express different combinations of known markers of layer 1 interneurons, including cholecystokinin (CCK), reelin (RELN), neuron derived neurotrophic factor (NDNF), and lysosomal associated membrane protein family member 5 (LAMP), many of which were confirmed to have expression in layer 1 by ISH”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
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“Iterative clustering was used to group nuclei with similar transcriptional profiles, thereby identifying a robust set of transcriptomic-defined cell types”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
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“Remarkably, this immunohistochemical profile aligned closely with a single transcriptomic cell type, i5, which was similarly GAD1/CCK-positive but CNR1/SST/CALB2/PVALB-negative (Fig.3B, red box).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“We found that RCs were involved in single cell activated ensembles detected through disynaptic IPSPs triggered by layer 2 (n=1) and layer 3 (n=2) pyramidal cells and polysynaptic EPSPs triggered by an axo-axonic cell, respectively (data not shown).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
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“This putative rosehip transcriptomic type, one of the most distinctive layer 1 GABAergic transcriptomic types, expresses many other genes either highly specifically or coexpressed in only one other layer 1 cell type.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“The size of active zones in RCs (0.11±0.03 µm2, n=11) was not correlated to bouton volumes (rho=0.34, p=0.29, Spearman correlation).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“Measurements based on serial section electron microscopy and three-dimensional reconstructions revealed that the volume of boutons of RCs (0.37±0.18 µm3, n=31) was approximately four times larger (p<0.001; MW U-test) compared to that of NGFCs (0.08±0.06 µm3, n=24, Fig.2E).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“IPSPs elicited by RCs were mediated by GABAA receptors based on experiments showing blockade of IPSPs by application of the GABAA receptor antagonist gabazine (n=4, 10 µM, Fig.5G).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
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“Changes in ΔF/F (17.2±7.3%) in distal branches of the apical dendrites in layer 1 were consistently detected at multiple (17±8) locations on the postsynaptic neurons confirming action potential backpropagation into distal apical dendritic branches of human pyramidal cells”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
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“Inputs from RCs simultaneous with backpropagating action potentials were effective in suppressing the amplitude of Ca2+ signals relative to control (n=6, 12.8±4.6% vs. 18.8±5.7% ΔF/F, p<0.02, Wilcoxon-test, Fig.6C)”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
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“Amplitudes of RC triggered IPSPs arriving to interneurons (0.428±0.370 mV) were larger compared to those targeting layer 3 pyramidal cells (0.087±0.059 mV, p<0.05, MW U-test)”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
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“The amplitude of the IPSPs triggered by the first action potential of RCs and evoked on distal dendrites of the postsynaptic pyramidal was (35.6±24.7 µV) at the soma”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
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“Impedance at the lowest frequency (Z0.2Hz) was similar in layer 1 interneurons (rosehip, 258±81 MΩ, neurogliaform, 279±128 MΩ, unclassified, 261±133 MΩ, Lillefors test followed by one-way ANOVA with Bonferroni correction).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
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“However, the amplitude of the sag measured in anatomically classified RCs (1.73±0.30, n=55) exceeded that of interneurons morphologically identified as NGFCs (1.19±0.12, n=16, p<0.001, Wilcoxon-test) or unclassified interneurons (1.29±0.28, n=36, p<0.001, Wilcoxon-test).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
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“the output of RCs were predominantly directed towards layer 3 pyramidal cells (n=16, CR 46%) having somata >70 µm below the layer 1/2 border.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
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“All fully reconstructed boutons (n=31) formed single synapses targeting dendritic shafts.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“The power of averaged fast Fourier transforms (FFT) of subthreshold membrane potential oscillations27 was higher between 3.8 and 80 Hz in RCs compared to neurogliaform and other interneurons”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
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“This diversity also appears to be higher than described for layer 1 in mouse4, although by covering all layers that study likely underrepresented layer 1.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [4] Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016). source
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“Analysis of silent and suprathreshold periods during rheobasic firing of RCs indicated that membrane oscillations and firing of RCs were tuned to beta and gamma frequencies”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
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“We did not find significant differences between NGFCs and unclassified interneurons in impedance parameters.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
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“The proportion of GAD1+ cells that are PDGFRA+/TRPC3+ was ~10%, therefore a lower bound.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“Many other rosehip-selective genes had no evidence of expression in layer 1 interneurons in mouse based on single cell transcriptomics (Fig.3B, Suppl. Fig.5B).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“Axon tortuosity (see Methods) of RCs (1.42±0.05) was similar to that of neurogliaform (1.54±0.15) and BCs (1.31±0.10).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“intraburst frequency of stuttering firing also peaked in the beta-gamma range”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
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“Many rosehip marker genes are not expressed in Smad3 or other Pvalb/Sst/Vip-negative mouse cell types (Fig.3B, right panel) or the complete set of mouse GABAergic types (Suppl. Fig.5B, right panel).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“Presynaptic layer 1 interneurons were connected to RCs with an overall coupling ratio (CR) of 45%.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
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“when randomly sampling the output formed by RCs (n=6) using serial electron microscopic sections, we found that axon terminals (n=64) exclusively targeted dendritic shafts”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
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“RC axons branched more frequently, with RCs, NGFCs and BCs having 1.52±0.45, 0.61±0.21 and 0.52±0.10 nodes along 100 µm length of their axons (p<0.005 for both, MW U-test).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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“Anatomically identified RCs responded to long (800 ms) suprathreshold current injections with stuttering or irregular spiking firing patterns2 when activated from resting membrane potential (-61.34±5.8 mV, Fig.4A).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
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“Very large unitary EPSPs, described to drive human basket and axo-axonic cells to suprathreshold postsynaptic responses10,11,14, were not encountered on RCs.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
What the sources say
- Not checked yetcites [10] Molnár, G. et al. Complex events initiated by individual spikes in the human cerebral cortex. PLoS Biol. 6, e222 (2008). source
- Not checked yetcites [11] Molnár, G. et al. Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles. eLife 5, e18167 (2016). source
- Not checked yetcites [14] Szegedi, V. et al. Plasticity in single axon glutamatergic connection interneurons regulates complex events in the human neocortex to GABAergic. PLoS Biol. 14, e2000237 (2016). source
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“coupling coefficients for gap junctions (0.05±0.05) were similar to those found earlier between human and rodent interneurons23.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
What the sources say
- Not checked yetcites [23] Oláh, S. et al. Output of neurogliaform cells to various neuron types in the human and rat cerebral cortex. Front. Neural Circuits 1, 4 (2007). source
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In the paper
“Resonance magnitude (Q, see methods) of RCs (1.77±0.34) was significantly higher compared to NGFCs (1.31±0.07; p<0.021, Lillefors test followed by one way ANOVA with Bonferroni correction) and unclassified interneurons (1.37±0.19; p<0.049).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
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In the paper
“RCs established 2.6±1.5 (range, 1-4) close appositions on dendrites of layer 3 pyramidal cells at distances 290±98 µm (range, 94-455 µm) from the somata of postsynaptic pyramidal cells (n=5).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
plainn = 5- Asserted: passes — The authors put it forward as true.
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In the paper
“In turn, monosynaptic output connections triggered by anatomically (n=49) and SVM (n=13) identified RCs rarely innervated postsynaptic interneurons (overall CR 8%).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
plainn = 197- Asserted: passes — The authors put it forward as true.
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In the paper
“We found correlation between the rise times of IPSPs arriving to the postsynaptic pyramidal cells (n=5, 7.3±2.4 ms, range 3.8-10.1 ms) and the distances of close axo-dendritic appositions from the somata (ρ=0.90, P= 0.037, Spearman correlation).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
plaincorrelationaln = 5 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“The standard deviation of interspike intervals was higher in RCs (87±64 ms, n=55) compared to neurogliaform (41±34 ms, n=16, p<0.001, Wilcoxon-test) or unclassified (47±41 ms, n=36, p<0.001, Wilcoxon-test) interneurons”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
plaincorrelationaln = 55 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“We found that GAD1+ cells expressing rosehip marker genes with low or absent expression of CNR1 were present in layer 1 of both BA9 and BA40”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
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In the paper
“The best feature set consisted of 2 features, the maximal standard deviation of interspike-intervals (ISI SD) and the amplitude of sag in response to hyperpolarization (-100 pA).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Firing classification analysis
plainn = 55- Asserted: passes — The authors put it forward as true.
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In the paper
“The fluorescence intensity of cells measured positive and negative with this method were significantly different (p<0.01, MW U-test).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Immunohistochemistry of biocytin-labeled cells
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
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In the paper
“To our knowledge, interneurons having the phenotype of RCs detailed below have not been identified previously in layer 1 of the cerebral cortex.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
hedgedn = 10- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Single cell transcriptomics enables unbiased, high-throughput quantitative surveys of molecularly defined cell types4–6 that can be applied to any species including human.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
What the sources say
- Not checked yetcites [4] Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016). source
- Not checked yetcites [5] Zeisel, A. et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347, 1138–1142 (2015). source
- Not checked yetcites [6] Macosko, E. Z. et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“To our knowledge a similar anatomical cell type has not been described in rodent.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
hedged- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Support vector machine (SVM)-based wrapper feature selection of electrophysiological parameters ranked the amplitude of the sag and the standard deviation of interspike intervals as the two best delineators out of n=200 measured electrophysiological parameters for separating anatomically identified rosehip, neurogliaform and unclassified interneurons in layer 1”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
plaincorrelationaln = 107- Asserted: passes — The authors put it forward as true.
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In the paper
“In this respect, it appears similar to other highly specialized and distinctive cortical cell types such as chandelier cells39.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [39] Somogyi, P. A specific ‘axo-axonal’ interneuron in the visual cortex of the rat. Brain Res. 136, 345–350 (1977). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, it is the unique combinatorial expression of many marker genes that defines RCs.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The results above indicate that RCs in layer 1 might preferentially target pyramidal cells sending terminal branches of their apical dendrites to layer 1.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
hedgedcorrelationaln = 16- Asserted: passes — The authors put it forward as true.
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In the paper
“This difference is likely due to a combination of improved sequencing technique and increased sampling in a targeted anatomical domain enriched in GABAergic neurons.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, a recent characterization of rat cortex3 described 6 morphological and 17 morpho-electric types in layer 1, so our results are consistent with the neuronal diversity described using other methods.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [3] Markram, H. et al. Reconstruction and simulation of neocortical microcircuitry. Cell 163, 456–492 (2015). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we demonstrate the strength of a modern version of this approach that can be applied to human postmortem and neurosurgical tissues.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
boosted- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“the best hyperplane separating RCs from other interneuron types according to SVM analysis had a false positive rate of 0% for identifying RCs (n=37) in the total population of anatomically recovered layer 1 interneurons (n=107).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
plainn = 37- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, Lake et al.22 identified cluster IN4 (the best match to rosehip cluster i5) in all six cortical areas sampled (frontal, temporal, and visual cortex).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
What the sources say
- Not checked yetcites Lake et al.22 Lake, B. B. et al. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. Science 352, 1586–1590 (2016). source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Preferential placement of output synapses on distal dendritic shafts of pyramidal cells reaching layer 1 suggest that RCs might specialize in the control of dendritic signal processing.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
hedgedconditionaln = 5 ·- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, the rosehip molecular marker signature appears highly distinctive from any published data from rodent.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
hedged- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“RCs may be of particular importance in compartmental control of backpropagating action potentials and their pairing with incoming excitatory inputs.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the monosynaptic pyramidal cell-preferring pathway initiated by RCs does not appear to have a homologue in the rodent layer 1 circuit.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
hedged- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This allowed us to collect nuclei from high quality specimens that met stringent quality control metrics”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Statistics
plainn = 2- Asserted: passes — The authors put it forward as true.
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In the paper
“Using this Random Forest model applied to the entire layer 1 dataset including contaminating layer 2 excitatory and inhibitory nuclei, 79% of 1154 single nuclei samples passed quality control.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > RNA-Seq quality control
plainn = 1,154- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 32
- It may state two separate claims as one. 59
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recent systematic efforts have provided insight into the cellular composition and organization of rodent neocortical circuits, suggesting the presence of several dozen inhibitory and excitatory cell types3–5,7.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
What the sources say
- Not checked yetcites [3] Markram, H. et al. Reconstruction and simulation of neocortical microcircuitry. Cell 163, 456–492 (2015). source
- Supportedcites [4] Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016). source
The Abstract reports 23 GABAergic (inhibitory) and 19 glutamatergic (excitatory) transcriptomic cell types in adult mouse primary visual cortex—42 neuronal types in total. The Discussion describes this as a systematic taxonomy of cortical cell types, supporting the citing sentence’s hedged claim about several dozen types in rodent neocortex. (LLM, conf=0.92)
- Not checked yetcites [5] Zeisel, A. et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347, 1138–1142 (2015). source
- Partly supportedcites [7] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462 (2015). sourceExperimental — accuracy not yet measured
The Results report a systematic study of adult mouse neocortex that distinguished inhibitory and excitatory cell types. It identified 15 interneuron types and two pyramidal-neuron types in the layers studied, but does not establish the claimed total of several dozen across rodent neocortical circuits. (LLM, conf=0.88)
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A better understanding of human cellular and circuit organization may help counteract the current lack of success in translating promising rodent results to effective treatment against human neuropsychiatric disorders49,50.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [49] Mak, I. W., Evaniew, N. & Ghert, M. Lost in translation: animal models and clinical trials in cancer treatment. Am. J. Transl. Res. 6, 114–118 (2014).
- Partly supportedcites [50] Cavanaugh, S. E., Pippin, J. J. & Barnard, N. D. Animal models of Alzheimer disease: historical pitfalls and a path forward. ALTEX 31, 279–302 (2014). sourceExperimental — accuracy not yet measured
Section 8, “The path forward: humanizing AD research” (page unavailable), says animal models have largely failed to predict effective Alzheimer disease treatments and advocates research focused on human biology. It does not specifically propose understanding human cellular and circuit organization, and its argument concerns Alzheimer disease rather than neuropsychiatric disorders generally. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Thus, RCs may provide supplementary inhibitory control required to balance the potentially higher excitability in human dendrites8 and modulate interactions between long range excitatory connections arriving to layer 1 and backpropagating action potentials suggested to participate in interhemispheric modulation45.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Supportedcites [8] Eyal, G. et al. Unique membrane properties and enhanced signal processing in human neocortical neurons. eLife 5, e16553 (2016). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [45] Palmer, L. M. et al. The cellular basis of GABA(B)-mediated interhemispheric inhibition. Science 335, 989–993 (2012). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Therefore, there appear to be ten inhibitory cell types within layer 1, although it is not clear whether any of these types are completely restricted to layer 1.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“voltage-gated ion channels and GABA and glutamate receptor subunits show diverse expression patterns among interneurons, including highly cell type-specific expression of CACNA2D1, GABRG1, KCNH5, and SCN5A”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Light microscopic examination of these cells identified neurons with previously described morphological features, e.g. neurogliaform cells (NGFCs, n=16, 21%; Fig.2C,D)1,21,24 as well as a novel group of interneurons having large, rosehip-shaped axonal boutons forming very compact, bushy arborizations (rosehip cells, RCs, n=10, 13%; Fig.2A,D).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plainn = 76- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The bouton density of rosehip, neurogliaform and BCs almost monotonously decreased with increasing distances from the soma; however, bouton densities were lower in BCs 30-50 µm (p<0.04 for 30-50, MW U-test) and higher in NGFCs 70-220 µm (p<0.02, MW U-test) and in BCs 130-220 µm (p<0.03) from the soma.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Total dendritic length (1.96±0.90 mm) and dendritic node frequency per 100 µm (0.66±0.21) of RCs were significantly different from those of BCs (3.41±0.58 mm, p<0.031; 0.29±0.10, p<0.009, respectively, MW U-test) and were similar to those of NGFCs (2.62±1.08 mm, 1.50±1.47).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plainn = 6 ·- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Maximal radial extent of axon of RCs (263.42±69.09 µm) was significantly smaller than that of BCs (713.22±124.87 µm, p<0.005, MW U-test), but were not different from those of NGFCs (323.18±49.60 µm).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plainn = 5 ·- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of primary dendrites of RCs (5.50±1.87) was similar to that of BCs (6.2±2.17, n=5) and was significantly fewer compared to NGFCs (8.6±2.19, n=5, p<0.04, Mann-Whitney (MW) U-test).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plainn = 5 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These rosehip cells show an immunohistochemical profile (GAD1/CCK-positive, CNR1/SST/CALB2/PVALB-negative) matching a single transcriptomically-defined cell type”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“RCs had longer interbouton intervals compared to NGFCs (3.97±0.49 and 3.10±0.32 µm, respectively, p<0.038, MW U-test) and shorter compared to BCs (5.63±0.51 µm, p<0.024) measured as linear distances between neighboring boutons.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, both SST and VIP (but not PVALB) are seen in human MTG layer 1 by ISH”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“characterize a novel group of human interneurons with anatomical features never described in rodents having large, “rosehip”-like axonal boutons and compact arborization”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
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In the paper
“several of these markers appear to be related to interaction with endothelia, including endothelin receptor type A (EDNRA) and epidermal growth factor (EGF).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“The axon of RCs usually emerged from the basal part of the soma and gave rise to very compact, dense axonal trees predominantly arborizing in layer 1 with tortuous collaterals having spindle-shaped boutons with diameters not seen in other types of human layer 1 interneurons in our sample.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plainn = 10- Asserted: passes — The authors put it forward as true.
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In the paper
“cluster i2 represents a cell type restricted to layer 2 since it also expresses LHX6 which is not found in layer 1”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
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In the paper
“clusters corresponded to all major classes of neural cell types that were expected to be captured”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results
plainn = 2- Asserted: passes — The authors put it forward as true.
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In the paper
“Targeted recordings increased the number of RCs in our database (n=120)”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plaindirectn = 120- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Total length (11.13±1.99 mm) and maximal horizontal extent of axons (287.75±70.15 µm) of RCs were significantly smaller than those of NGFCs (24.74±8.90 mm, 648.68±202.60 µm, respectively; p<0.005 for both, MW U-test) and BCs (31.16±14.79 mm, p<0.009; 1102.76±296.99 µm, p<0.005, respectively, MW U-test).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plainn = 5 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“RCs received local excitatory inputs from layer 2-3 pyramidal cells sporadically (n=8, CR 5%) with monosynaptic EPSP amplitudes of 3.357±1.458 mV and paired pulse ratios of 0.68±0.12.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
plaincorrelationaln = 8- Asserted: passes — The authors put it forward as true.
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In the paper
“The RC represents a type with highly distinctive transcriptomic signature, a highly distinctive morphological, physiological and connectional phenotype, and a strong correspondence between these properties.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
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In the paper
“This revealed that RCs were immunopositive for CCK (n=10) but negative for CB1 cannabinoid receptor (CNR1, n=11), SST (n=9) and calretinin (CALB2; n=2; Fig.3A).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plainn = 10- Asserted: passes — The authors put it forward as true.
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In the paper
“frequencies of maximal impedance (fmax) in RCs (4.17±1.1 Hz) were significantly higher than in NGFCs (1.98±1.04 Hz; p<0.045) but the difference was not significant compared to unclassified interneurons (2.47±1.47 Hz, p<0.142).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
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In the paper
“Fast components of IPSPs arriving to RCs evoked by different presynaptic interneurons had similar amplitudes (0.982±0.705, 0.915±0.594 and 1.504±1.308 mV, respectively) and showed paired pulse depression with paired pulse ratios of (0.42±0.48, 0.27±0.04 and 0.71±0.26, respectively).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“time constants of RCs (7.3±3.7 ms) were similar to neurogliaform (8.9±2.4 ms, p<0.001) and faster compared to other cells (11.1±12.5 ms, p<0.001).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“application of the CB1 receptor antagonist AM251 was ineffective in modulating RC evoked IPSPs (n=4, Fig.5H), supporting our results of single cell digital PCR, IHC and ISH data (Fig.3).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
plainn = 4- Asserted: passes — The authors put it forward as true.
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In the paper
“The targeted application of single nucleus sequencing reported here has demonstrated a significantly higher degree of GABAergic neuron complexity in just one layer of the human cerebral cortex (10 types) than what has previously been described in all of the cortex (8 types22).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [22] Lake, B. B. et al. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. Science 352, 1586–1590 (2016). source
boosted- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rosehip cluster i5 had a weak (r=0.34) reciprocal best match to mouse cluster Smad3, although several other human clusters (i7, i1, i4, i3) matched Smad3 almost as well (r>0.3).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“RCs also formed homologous electrical synapses (n=5, CR 57%) between each other (Fig.5K) and established convergent heterologous electrical synapses (n=2, CR 11%) with an unclassified layer 1 interneuron.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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In the paper
“Input resistances of RCs (139.6±54.1 MΩ) were similar to those of NGFCs (160.1±55.9 MΩ) and lower compared to other interneurons (216.3±84.4 MΩ, p<0.001, Wilcoxon-test)”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As predicted by the transcriptome data, RCs were positive for CCK, CPLX3, SV2C and TRPC3, and low (CNR1) or absent (NDNF) for genes not expressed by cells in that cluster”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“expression of LAMP5, SV2C, EYA4 and CPLX3 is seen by ISH in human layer 1 (Fig.3C); similarly, as predicted by transcriptomics three of these four genes are also expressed in mouse layer 1 whereas cells expressing Eya4 are extremely rare.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Rosehip inputs simultaneous with backpropagating pyramidal action potentials were effective in suppressing Ca2+ signals only at sites that were neighboring (8±5 µm) to the putative synapses between the two cells. No effect of RCs was detected at dendritic sites one step further in distance (21±14 µm, Fig.6D-F).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
plaindirectn = 4 ·- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed CCK+/CNR1-/LAMP5+, CCK+/PDGFRA+/SOX13+, and CCK+/TRPC3+/CPLX3+ cells, as well as cells where CCK was swapped with other positive rosehip markers”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Expression correlations were quite low (r < 0.5), and clusters could only be reliably grouped into broad classes of cell types.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Backpropagation of action potentials to dendrites of human neurons has been shown in previous studies13,29 and we confirmed these results by detecting dendritic Ca2+ responses following somatically elicited burst firing (100 ms current injections, 4 spikes/burst) in layer 3 pyramidal cells.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
What the sources say
- Not checked yetcites [13] Verhoog, M. B. et al. Mechanisms underlying the rules for associative plasticity at adult human neocortical synapses. J. Neurosci. 33, 17197–17208 (2013). source
- Not checked yetcites [29] Kerekes, B. P. et al. Combined two-photon imaging, electrophysiological, and anatomical investigation of the human neocortex in vitro. Neurophotonics 1, 011013 (2014). source
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The remaining n=5 (11 %) dendrites had no spines and received asymmetric synapses on the shaft were likely to be formed by interneurons.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
hedgedcorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“GABAergic cells evoking IPSPs on RCs included layer 1 NGFCs (n=10, CR 100 %), RCs (n=2, CR 17%) and unclassified interneurons (n=14, CR 40%); however, none of the tested interneurons (n=9) having somata in layer 2 (defined as <70 µm below the layer 1/2 border) were connected to RCs.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
plainn = 10- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“further ultrastructural analysis of postsynaptic dendrites (n=46) revealed dendritic spines and sparse innervation by symmetrical synapses on the shaft, suggesting that these dendrites belonged to pyramidal cells (n=41, 86%, Fig.5J).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
hedgedcorrelationaln = 46- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The triple positive cells for this combination were sparsely distributed across layer 1, although not restricted to this layer (Suppl. Fig.5D).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“PDGFRA+ cells represent ~15% of GAD1+ cells, therefore an upper bound.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, RCs were immunopositive for gamma-aminobutyric acid (GABA; n=2), for chicken ovalbumin upstream promoter transcription factor II (NR2F2; n=2) and negative for parvalbumin (n=3), neuronal nitric oxide synthase (n=4), neuropeptide Y (n=2), calbindin (n=2), and choline acetyltransferase (n=3; Suppl. Fig.5A).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plainn = 2- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Human clusters i5, i7, i1, i4, and i3 matched mouse Smad3+ and Ndnf+ clusters. Clusters i6, i8, i9, i11, and i10 matched mouse Vip+ clusters, and cluster i2 matched mouse Sst+ clusters.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Membrane properties of human neurons did not show significant changes for up to 20 h after slicing”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Electrophysiological recordings
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, RCs are CCK-positive but cannabinoid receptor-negative, and appear to selectively target distal dendrites of pyramidal neurons.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“confirming that transcriptomic clusters were consistent between donors and not driven by technical artifacts.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Statistics
boostedn = 2- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 408 GAD1+ cells were identified from two individuals for this quantification.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Multiplex fluorescent in situ hybridization (FISH)
plainn = 2- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed there is evidence for significant neuronal differences between rodents and human; for example, distinct membrane8,9 and synaptic10–14 properties and dendritic complexity15–17 of human neurons might contribute to human specific signal processing.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Abstract
What the sources say
- Not checked yetcites [8] Eyal, G. et al. Unique membrane properties and enhanced signal processing in human neocortical neurons. eLife 5, e16553 (2016). source
- Not checked yetcites [9] Wang, B. et al. A subtype of inhibitory interneuron with intrinsic persistent activity in human and monkey neocortex. Cell Rep. 10, 1450–1458 (2015). source
- Not checked yetcites [10] Molnár, G. et al. Complex events initiated by individual spikes in the human cerebral cortex. PLoS Biol. 6, e222 (2008). source
- Not checked yetcites [11] Molnár, G. et al. Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles. eLife 5, e18167 (2016). source
- Not checked yetcites [12] Testa-Silva, G. et al. Human synapses show a wide temporal window for spike-timing-dependent plasticity. Front. Synaptic Neurosci. 2, 12 (2010).
- Not checked yetcites [13] Verhoog, M. B. et al. Mechanisms underlying the rules for associative plasticity at adult human neocortical synapses. J. Neurosci. 33, 17197–17208 (2013). source
- Not checked yetcites [14] Szegedi, V. et al. Plasticity in single axon glutamatergic connection interneurons regulates complex events in the human neocortex to GABAergic. PLoS Biol. 14, e2000237 (2016). source
- Not checked yetcites [15] Elston, G. N. Pyramidal cells of the frontal lobe: all the more spinous to think with. J. Neurosci. 20, RC95 (2000). source
- Not checked yetcites [16] Morales, J. et al. Random positions of dendritic spines in human cerebral cortex. J. Neurosci. 34, 10078–10084 (2014). source
- Not checked yetcites [17] Mohan, H. et al. Dendritic and axonal architecture of individual pyramidal neurons across layers of adult human neocortex. Cereb. Cortex 25, 4839–4853 (2015). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Together, these data strongly link the anatomically-defined rosehip phenotype with a highly distinctive transcriptomic cell type signature that is found in human but apparently not in mouse layer 1.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the transcriptomic comparison is between human temporal cortex and mouse visual cortex, regional differences seem unlikely to account for this difference as we found the anatomically defined rosehip type in multiple human regions.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Quantification of cell proportions using marker expression is complicated by two factors; first, markers for one cell type are often expressed in others, and second, individual markers are often not expressed in every cell in a cluster.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Rosehip cells: novel morphological features in layer 1 of the human cerebral cortex
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“It is widely accepted28 that CCK-positive cells in the rodent show selectively high expression of cannabinoid receptors and are involved in perisomatic inhibition.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [28] Katona, I. & Freund, T. F. Multiple functions of endocannabinoid signaling in the brain. Annu. Rev. Neurosci. 35, 529–558 (2012). source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, local inputs to RCs appear to be predominantly GABAergic, acknowledging that some axon collaterals of pyramidal cells were cut during the slicing procedure (Fig.5C) leading to a potential underrepresentation of pyramidal cell triggered EPSPs.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together these approaches provide convergent evidence for robust cell type identities and concomitant evidence for species conservation or specialization.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Specimens were further screened for RNA quality and had an RNA integrity number (RIN) ≥7.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Postmortem human brain specimens
plainn = 2- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
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In the paper
“All human specimens were controls (nonpathological) and were therefore allocated into the same experimental group.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Statistics
plainn = 2- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Positive controls (10 nuclei pools and/or 10 pg and 1 pg total RNA) were included on every 96-well plate of sorted nuclei.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Nuclei isolation and FACS
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Using this Random Forest classification model, all 196 samples in the training set were classified correctly with high confidence scores.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > RNA-Seq quality control
plainn = 196- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sweeps were discarded with less than 5 spikes for the calculation of ISI SD.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Firing classification analysis
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Action potentials backpropagate to distal dendrites of human pyramidal cells and can be attenuated by RC activation.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Application of the random forest model to these test Pass and Fail samples resulted in only 8 misclassifications (4.9%), for a classification accuracy of 95%.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > RNA-Seq quality control
plainn = 185- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“our sample sizes are similar to those reported in previous publications10,11,14.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Statistics
What the sources say
- Not checked yetcites [10] Molnár, G. et al. Complex events initiated by individual spikes in the human cerebral cortex. PLoS Biol. 6, e222 (2008). source
- Not checked yetcites [11] Molnár, G. et al. Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles. eLife 5, e18167 (2016). source
- Not checked yetcites [14] Szegedi, V. et al. Plasticity in single axon glutamatergic connection interneurons regulates complex events in the human neocortex to GABAergic. PLoS Biol. 14, e2000237 (2016). source
plainn = 2- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The bouton morphology and/or the compact axonal field of RCs resembles that of cell types described in deeper layers of the cat cortex that innervate relatively proximal dendrites (dendrite targeting and clutch cells)40,41.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [40] Tamás, G., Buhl, E. H. & Somogyi, P. Fast IPSPs elicited via multiple synaptic release sites by different types of GABAergic neuron in the cat visual cortex. J. Physiol. (Lond.) 500, 715–738 (1997). source
- Not checked yetcites [41] Kisvárday, Z. F., Martin, K. A. C., Whitteridge, D. & Somogyi, P. Synaptic connections of intracellularly filled clutch cells: a type of small basket cell in the visual cortex of the cat. J. Comp. Neurol. 241, 111–137 (1985). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data collection and analysis were not performed blind to the conditions of the experiments.”
- Also stated in: § Statistics · plain
“data collection and analysis were not performed blind to the conditions of the experiments.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Electrophysiological recordings
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Statistics · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In total, 443/470 (94.3%) of nuclei were defined as core.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Cluster visualization
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Positive controls (POLR2A, UBC and PPIB) were used on each tissue sample to ensure RNA quality (ACD Bio, 320861).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Multiplex fluorescent in situ hybridization (FISH)
What the sources say
- Not checked yetcites ACD Bio, 320861
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The tissue specimens used in this study were pre-screened for known neuropsychiatric and neuropathological history, and underwent routine serological testing and toxicology screening.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Postmortem human brain specimens
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No data with successful quality control were excluded from the analyses.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Statistics
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The sharp resonance in the theta-range detected in individual RCs and its potential spread through gap junctions to a rosehip network could phase-selectively interact with long range inputs similarly to mechanisms suggested for example in oscillation dependent memory consolidation30,46.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [30] Freund, T. F. & Buzsáki, G. Interneurons of the hippocampus. Hippocampus 6, 347–470 (1996). source
- Not checked yetcites [46] Klausberger, T. & Somogyi, P. Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321, 53–57 (2008). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“recordings included in the analysis were arbitrarily terminated 15 h after slice preparation.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Electrophysiological recordings
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All tissue collection was performed in accordance with the provisions of the Uniform Anatomical Gift Act described in Health and Safety Code §§ 7150, et seq., and other applicable state and federal laws and regulations.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Postmortem human brain specimens
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The uniquely small membrane capacitance (Cm) found in human pyramidal cells8 promotes backpropagation of action potentials and increases excitability in human dendrites13,29 relative to rodent dendrites having larger Cm.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [8] Eyal, G. et al. Unique membrane properties and enhanced signal processing in human neocortical neurons. eLife 5, e16553 (2016). source
- Not checked yetcites [13] Verhoog, M. B. et al. Mechanisms underlying the rules for associative plasticity at adult human neocortical synapses. J. Neurosci. 33, 17197–17208 (2013). source
- Not checked yetcites [29] Kerekes, B. P. et al. Combined two-photon imaging, electrophysiological, and anatomical investigation of the human neocortex in vitro. Neurophotonics 1, 011013 (2014). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The function of neuron types specific to the human circuit could be important in understanding pathological alterations of network functions.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No sample-size calculation was performed”
- Also stated in: § Statistics · plain
“No statistical methods were used to pre-determine sample sizes”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Statistics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Statistics · plain
In the paper
“To remove data from low quality nuclei samples prior to downstream analysis, we implemented a Random Forest machine learning classification approach as described in detail in Aevermann et al. 58.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > RNA-Seq quality control
What the sources say
- Not checked yetcites [58] Aevermann, B. et al. Production of a preliminary quality control pipeline for single nuclei RNA-seq and its application in the analysis of cell type diversity of post-mortem human brain neocortex. Pac. Symp. Biocomput. 22, 564–575 (2017).
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To assess the robustness of clusters, the iterative clustering procedure described above was repeated 100 times for random subsamples of 80% of nuclei.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Clustering nuclei
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
In the paper
“Data from low quality nuclei samples was removed prior to downstream analysis, using a Random Forest machine learning classification approach as described58.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Statistics
What the sources say
- Not checked yetcites [58] Aevermann, B. et al. Production of a preliminary quality control pipeline for single nuclei RNA-seq and its application in the analysis of cell type diversity of post-mortem human brain neocortex. Pac. Symp. Biocomput. 22, 564–575 (2017).
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Addition of new human cell types, or specialization of existing types through major modification of cellular features, would be expected to alter circuit function3,43,44, and therefore cannot be studied in rodents.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [3] Markram, H. et al. Reconstruction and simulation of neocortical microcircuitry. Cell 163, 456–492 (2015). source
- Not checked yetcites [43] Tremblay, R., Lee, S. & Rudy, B. GABAergic interneurons in the neocortex: from cellular properties to circuits. Neuron 91, 260–292 (2016). source
- Not checked yetcites [44] Gjorgjieva, J., Drion, G. & Marder, E. Computational implications of biophysical diversity and multiple timescales in neurons and synapses for circuit performance. Curr. Opin. Neurobiol. 37, 44–52 (2016). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“reactions having CT values less than 23 or greater than 33 were considered primer dimers or background signals, respectively, and excluded from the data set.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Single cell reverse transcription and digital PCR
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The Western Institutional Review Board reviewed tissue collection processes and determined that they did not constitute human subjects research requiring IRB review.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Postmortem human brain specimens
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Randomization was not used.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Statistics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, several highly selective markers for RCs have been implicated as risk factors for neuropsychiatric disease, including netrin G1 (NTNG1) for Rett syndrome47 and neurotrypsin (PRSS12) for mental retardation48.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [47] Borg, I. et al. Disruption of Netrin G1 by a balanced chromosome translocation in a girl with Rett syndrome. Eur. J. Hum. Genet. 13, 921–927 (2005). source
- Not checked yetcites [48] Molinari, F. et al. Truncating neurotrypsin mutation in autosomal recessive nonsyndromic mental retardation. Science 298, 1779–1781 (2002). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Moreover, when assessing layer 1 canonical inhibitory pathways in rodent with high throughput electrophysiology capable of sampling all cell types in layer 1, Lee at al.42 found two interneuron types and two canonical pathways involving feed forward interneuron-to-interneuron connections.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [42] Lee, A. J. et al. Canonical organization of layer 1 neuron-led cortical inhibitory and disinhibitory interneuronal circuits. Cereb. Cortex 25, 2114–2126 (2015). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, focal intralayer inhibition restricted by the compact axonal arbor of RCs to distal dendrites of a column of pyramidal cells is also missing from the rodent; rather, mouse feedforward inhibitory connections are vertically spread to all somatodendritic domains42.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Discussion
What the sources say
- Not checked yetcites [42] Lee, A. J. et al. Canonical organization of layer 1 neuron-led cortical inhibitory and disinhibitory interneuronal circuits. Cereb. Cortex 25, 2114–2126 (2015). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Patients with a history of epilepsy were excluded from this study.”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Electrophysiological recordings
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The authors state this as an assumption.
Conservation of cellular and circuit principles in human cortex is assumed but largely untested.
“However, conservation of cellular and circuit principles in human cortex is assumed but largely untested to date.”
The paper relies on this without support.
Layer 1 of the middle temporal gyrus is expected to predominantly contain inhibitory neurons.
“microdissected layer 1 of the middle temporal gyrus, expected to predominantly contain inhibitory neurons”
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?
In the citing paper
“The cellular organization of interneuron diversity is remarkably similar between mouse and human, but there are important differences in the morphology, gene expression, laminar distribution and proportions of certain types of interneurons (Boldog et al., 2018; DeFelipe, 1997; Hodge et al., 2018).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Boldog et al., 2018
In the citing paper
“these cells are expected to have the Sst-Chodl t-type, linked to deep long-range projecting interneurons12,14,36,37 (Fig. 7h).”
From Classification of electrophysiological and morphological neuron types in the mouse visual cortex (2019) · cites this paper as [36]
In the citing paper
“Notably, this approach provides the means to evaluate and compare the circuit contributions and function of PV cINs across species, regardless of their genetic accessibility44,45.”
From Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans (2020) · cites this paper as [45]
In the citing paper
“A small sample size in a single cell genomics study does affect statistical power, but does not preclude the possibility of drawing meaningful inferences of cell type gene expression in the human brain (9,41) .”
From Single cell transcriptome profiling of the human alcohol-dependent brain (2020) · cites this paper as [41]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“postsynaptic dendrites (n=46) revealed dendritic spines and sparse innervation by symmetrical synapses on the shaft, suggesting that these dendrites belonged to pyramidal cells (n=41, 86%, Fig.5J).”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Function of rosehip cells in local microcircuits
Reported 86 · recomputed 89.130435
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Results > Intrinsic electrophysiological properties of rosehip cells
“time constants of RCs (7.3±3.7 ms) were similar to neurogliaform (8.9±2.4 ms, p<0.001)”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Electrophysiological recordings
“differences were considered significant if p<0.05.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“Template cDNA was supplemented with nuclease free water to a final volume of 8 μl. 2 μl TaqMan Assays (Thermo Fisher), 10 μl OpenArray Digital PCR Master Mix (Thermo Fisher, Cat.No.: 4458095) and nuclease free water (3 μl) were mixed to obtain a total volume of 20 μl”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Single cell reverse transcription and digital PCR
Reported 20 · recomputed 23
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Measurement of impedance profile
“For statistical comparison of the impedance profiles, four parameters were considered:”
§ Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type > Methods > Measurement of impedance profile
“impedance at lowest frequency (Z0.2Hz); resonance magnitude (Q, the impedance magnitude at the resonance peak i.e. maximal impedance value divided by the impedance magnitude at the lowest input frequency of 0.2 Hz); and the frequency at maximum impedance (fmax).”
Citations
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Conserved cell types with divergent features in human versus mouse cortex
Hodge, R. D., Bakken, T. E., Miller, J. A., Smith, K. A., Barkan, E. R., Graybuck, L. T., Close, J. L., Long, B., Johansen, N., Penn, O., et al. (2019) · Nature · doi:10.1038/s41586-019-1506-7 · Cited by 1,775
Self-citationComparative cellular analysis of motor cortex in human, marmoset and mouse
Bakken, T. E., Jorstad, N. L., Hu, Q., Lake, B. B., Tian, W., Kalmbach, B. E., Crow, M., Hodge, R. D., Krienen, F. M., Sorensen, S. A., et al. (2021) · Nature · doi:10.1038/s41586-021-03465-8 · Cited by 812
Self-citationDevelopment and Functional Diversification of Cortical Interneurons
Lim, L., Mi, D., Llorca, A., & Marín, O. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.009 · Cited by 714
Dendritic action potentials and computation in human layer 2/3 cortical neurons
Gidon, A., Zolnik, T. A., Fidzinski, P., Bolduan, F., Papoutsi, A., Poirazi, P., Holtkamp, M., Vida, I., & Larkum, M. E. (2020) · Science · doi:10.1126/science.aax6239 · Cited by 599
Classification of electrophysiological and morphological neuron types in the mouse visual cortex
Gouwens, N. W., Sorensen, S. A., Berg, J., Lee, C., Jarsky, T., Ting, J., Sunkin, S. M., Feng, D., Anastassiou, C. A., Barkan, E., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0417-0 · Cited by 456
Self-citation
Metadata
- Authors
- Boldog, E., Bakken, T. E., Hodge, R. D., Novotny, M., Aevermann, B. D., Baka, J., Bordé, S., Close, J. L., Diez-Fuertes, F., Ding, S.-L., Faragó, N., Kocsis, Á. K., Kovács, B., Maltzer, Z., McCorrison, J. M., Miller, J. A., Molnár, G., Oláh, G., Ozsvár, A., Rózsa, M., Shehata, S. I., Smith, K. A., Sunkin, S. M., Tran, D. N., Venepally, P., Wall, A., Puskás, L. G., Barzó, P., Steemers, F. J., Schork, N. J., Scheuermann, R. H., Lasken, R. S., Lein, E. S., & Tamás, G.
- Affiliations
- University of Szeged (HU)
- Allen Institute for Brain Science (US)
- J. Craig Venter Institute (US)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- Illumina (United States) (US)
- Corresponding author
- Lein, Ed S.
- Tamás, Gábor
- ORCID
- Boldog, Eszter
- Bakken, Trygve E.
- Hodge, Rebecca D.
- Novotny, Mark
- Aevermann, Brian D.
- Baka, Judith
- Bordé, Sándor
- Close, Jennie L.
- Ding, Song-Lin
- Faragó, Nóra
- Kocsis, Ágnes K.
- Kovács, Balázs
- Maltzer, Zoe
- McCorrison, Jamison M.
- Miller, Jeremy A.
- Molnár, Gábor
- Oláh, Gáspár
- Ozsvár, Attila
- Rózsa, Márton
- Shehata, Soraya I.
- Smith, Kimberly A.
- Sunkin, Susan M.
- Puskás, László G.
- Barzó, Pál
- Schork, Nicholas J.
- Scheuermann, Richard H.
- Lein, Ed S.
- Tamás, Gábor
- Venue
- Nature Neuroscience
- Published
- 2018-08-27
- Volume
- 21
- Issue
- 9
- Pages
- 1185-1195
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6130849
- OpenAlex
- W2767443671
- Semantic Scholar
- 3ae2f32de897a98351ded7a44ee959ad0bc0de3d
- Cited by
- 291
- References
- 73
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 28 · 2023: 58 · 2022: 27 · 2021: 31 · 2020: 44 · 2019: 43 · 2018: 10
- FWCI
- 14.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Magyar Tudományos Akadémia
- National Institutes of Health (5u01mh114812-03)
- National Research, Development and Innovation Office (14-1-2015-0155)
- National Institute of Mental Health (U01MH114812)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- GABAergic interneurons, human cortex, interneuron subtypes, single-nucleus RNA sequencing, axonal boutons, dendritic branching, dendritic computation, GAD1, cholecystokinin, CNR1, parvalbumin
- MeSH terms
- Adult, Aged, Axons, Cerebral Cortex, Humans, Male, RNA, Gene Library, Polymerase Chain Reaction, Sequence Analysis, RNA, Gap Junctions, Presynaptic Terminals, Pyramidal Cells, Dendritic Spines, GABAergic Neurons, Transcriptome
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