The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index; 5 of the 66 sources its claims cite were checked for support.
Classification of electrophysiological and morphological neuron types in the mouse visual cortex
Open accessPublished version of a preprint
Abstract
Understanding the diversity of cell types in the brain has been an enduring challenge and requires detailed characterization of individual neurons in multiple dimensions. To systematically profile morpho-electric properties of mammalian neurons, we established a single-cell characterization pipeline using standardized patch-clamp recordings in brain slices and biocytin-based neuronal reconstructions. We built a publicly accessible online database, the Allen Cell Types Database, to display these datasets. Intrinsic physiological properties were measured from 1,938 neurons from the adult laboratory mouse visual cortex, morphological properties were measured from 461 reconstructed neurons, and 452 neurons had both measurements available. Quantitative features were used to classify neurons into distinct types using unsupervised methods. We established a taxonomy of morphologically and electrophysiologically defined cell types for this region of the cortex, with 17 electrophysiological types, 38 morphological types and 46 morpho-electric types. There was good correspondence with previously defined transcriptomic cell types and subclasses using the same transgenic mouse lines. Gouwens et al. established a morpho-electrical taxonomy of cell types for the mouse visual cortex via unsupervised clustering analysis of multiple quantitative features from 1,938 neurons available online at the Allen Cell Types Database.
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TL;DR
This paper presents a standardized patch-clamp and biocytin-reconstruction pipeline to classify neurons in adult mouse visual cortex, yielding 17 electrophysiological types, 38 morphological types, and 46 joint morpho-electric types. The joint types align better with transcriptomic subclasses than either modality alone, and the data and tools are publicly released.
Key findings
- From 1,938 neurons passing electrophysiology QC (928 spiny/excitatory, 1,010 aspiny or sparsely spiny/inhibitory), 461 were reconstructed (254 spiny, 207 aspiny/sparsely spiny), and 452 had both modalities; unsupervised clustering identified 17 e-types (4 excitatory, 13 inhibitory), 38 m-types (19 spiny, 19 aspiny), and 46 me-types (20 excitatory, 26 inhibitory).
- Joint clustering produced 46 me-types rather than the 120 simple intersections of e-types and m-types, and these me-types showed stronger consistency with transcriptomic subclasses than e-types or m-types alone.
- Morphological features were more informative for excitatory me-types, while both electrophysiological and morphological features predicted many inhibitory me-types; selective transgenic line/layer combinations linked some me-types to specific transcriptomic types.
- The t-SNE projection separated excitatory and inhibitory cells and showed coherence by transgenic driver, with Pvalb, Sst, Vip, and Chat populations occupying related but distinct regions.
Methods
- Standardized in vitro pipeline: whole-cell current-clamp recordings from adult mouse visual cortex slices with biocytin-filled pipettes, fixed stimulus protocols (short and long current steps, ramps, noisy injections), quality-control criteria, transgenic Cre driver lines, and atlas mapping; most cells came from primary visual cortex (n=1,599).
- Electrophysiology features were reduced with sparse PCA and clustered using Gaussian mixture models with entropy-based merging and subsampling stability; morphology features from reconstructed dendrites and axons were clustered hierarchically with co-clustering; joint clustering combined both feature sets across multiple methods and weightings to derive consensus clusters.
- Transcriptomic correspondence was inferred using transgenic line/layer labels and prior FACS data from Tasic et al., with binary consistency scores for subclasses and selective line/layer combinations for transcriptomic types.
Limitations
- The authors state that electrophysiological results depend on their specific recording protocols and solutions; other protocols could reveal additional distinguishing features and require revising the taxonomy. They also note that their transgenic sampling strategy does not allow estimating relative proportions of cell types in the circuit, and they could not clearly link to the Sncg subclass, which they suspect was underrepresented.
- The authors acknowledge biases from chosen stimuli and quantified morphological features, and note that z-dimension-dependent morphological features were excluded because of slice z-compression, though they report that re-running clustering after volume restoration and alignment showed good agreement.
- Evident from the text: transgenic lines are imperfect proxies for transcriptomic identity, some me-types showed heterogeneity even among cells putatively from a single transcriptomic type, and morphological reconstructions were a selected subset rather than all recorded cells.
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Claims the paper makes
79 Own result · 33 Own method · 29 Not checked yet · 18 Own interpretation · 7 No basis given · 1 Supported · 1 Supported so far
Every source the paper cites for this claim was checked and supports it.
In the paper
“Chat cells, a subset of Vip cells12,25,26, were located within the broader region populated by the Vip cells near its border with excitatory cells.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
What the sources say
- Supportedcites [12] Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016). source
The citation is attached to the identification of Chat cells as a subset of Vip cells, not to the citing authors’ observation about their position near excitatory cells. In “Cortical cell types: markers and relationships” (page unavailable), the source identifies a Vip-Chat transcriptomic type within the Vip major type and reports Chat expression in Vip-positive cells. (LLM, conf=0.91)
- Supportedcites [25] Gonchar, Y., Wang, Q. & Burkhalter, A. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining. Front. Neuroanat. 1, 3 (2008). source
The Results section (‘PV-negative neurons fall into numerous discrete subgroups’; page unavailable) states that all ChAT neurons expressed VIP, while many VIP neurons lacked ChAT. This confirms the subset relationship to which the citation is attached. The sentence’s spatial description is not attributed to this citation. (LLM, conf=0.93)
- Supportedcites [26] von Engelhardt, J., Eliava, M., Meyer, A. H., Rozov, A. & Monyer, H. Functional characterization of intrinsic cholinergic interneurons in the cortex. J. Neurosci. 27, 5633–5642 (2007). source
The citation is attached to the statement that ChAT cells are a subset of VIP cells, not to the citing authors’ observation about their location. In the paper’s “ChAT and EGFP colocalize in the cortex with VIP and calretinin” section, 98% of ChAT-immunoreactive interneurons were VIP-immunoreactive, supporting that identification. (LLM, conf=0.92)
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- Supported
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
“Joint clustering based on combined electrophysiological and morphological data resulted in 46 me-types.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
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In the paper
“morphological properties were measured from 461 reconstructed neurons”
§ Classification of electrophysiological and morphological types in mouse visual cortex > Abstract
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Unsupervised clustering methods mapped neurons of the adult mouse visual cortex to 17 distinct electrophysiological or e-types and 38 morphological or m-types.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
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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
“Intrinsic physiological properties were measured from 1,938 neurons from the adult laboratory mouse visual cortex”
§ Classification of electrophysiological and morphological types in mouse visual cortex > Abstract
plainn = 1,938- Asserted: passes — The authors put it forward as true.
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In the paper
“452 neurons had both measurements available”
§ Classification of electrophysiological and morphological types in mouse visual cortex > Abstract
plain- Asserted: passes — The authors put it forward as true.
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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
“The use of transgenic labels established preliminary correspondences with major transcriptomic subclasses and specific transcriptomic types.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
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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
“found good correspondence with previously-defined transcriptomic cell types and subclasses using the same transgenic mouse lines”
§ Classification of electrophysiological and morphological types in mouse visual cortex > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This confirmed that morphological features were more distinguishing for excitatory me-type classification, while both electrophysiological and morphological features could accurately predict many inhibitory me-types.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Comparison to transcriptomic classification via transgenic lines
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Certain inhibitory m-types (e.g. Aspiny_4, Aspiny_8) were distributed across multiple me-types due to differences in electrophysiological properties.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Joint classification with electrophysiology and morphology
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- Probably not a substantial claim. 47
- It may state two separate claims as one. 55
- The quote only partly states this claim. 1
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
“Recent studies have defined taxonomies of mouse neocortical cell types by single-cell RNA-seq transcriptomic profiling of isolated neurons and glia12–14.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Comparison to transcriptomic classification via transgenic lines
What the sources say
- Supportedcites [12] Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016). source
The Abstract states that the study constructed a taxonomy of adult mouse primary visual cortex using single-cell RNA-seq, identifying neuronal and non-neuronal types. “Cortical cell types: markers and relationships” identifies the non-neuronal types, including astrocytes, microglia and oligodendrocytes. The cited paper is therefore an example of the studies described; the passages have no page numbers. (LLM, conf=0.94)
- Not checked yetcites [13] Zeisel, A. et al. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347, 1138–1142 (2015). source
- Supportedcites [14] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source
The Abstract states that the study defined 133 transcriptomic cell types by single-cell RNA sequencing of adult mouse neocortex. The Overall cell type taxonomy section says the cells were isolated and identifies both neuronal and non-neuronal types; Extended Data Fig. 9 identifies glial types among the latter. This paper is therefore an example of the studies described in the citing sentence. Page numbers are not provided in our copy. (LLM, conf=0.94)
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In the paper
“Most cells (n=1,599) were from primary visual cortex (VISp); the remainder were in nearby higher visual areas.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Creating the in vitro single cell characterization platform
plainn = 1,599- Asserted: passes — The authors put it forward as true.
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In the paper
“The experimental data and analysis tools are made available as a public resource as part of the Allen Cell Types Database and the Allen Software Development Kit.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
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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
“We built a publicly-accessible online database, the Allen Cell Types Database, to display these data sets.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > Abstract
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 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 established a taxonomy of morphologically- and electrophysiologically-defined cell types for this region of cortex with 17 e-types, 38 m-types, and 46 me-types”
§ Classification of electrophysiological and morphological types in mouse visual cortex > Abstract
plainn = 1,938- Asserted: passes — The authors put it forward as true.
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In the paper
“We applied a sparse principal components analysis20,21 (sPCA) procedure to each collected subset of the data, which typically identified 1-8 components that exceeded an adjusted explained variance threshold per subset”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“As of this writing, 1,861 out of 1,938 cells had electrophysiological data on the website, and 431 out of 461 reconstructions were on the website.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Creating the in vitro single cell characterization platform
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In the paper
“we identified spiny clusters that subdivided the BBP qualitative m-types (e.g., the single L2/3 PC m-type was split into 6 m-types), and those that merged m-types (e.g., L5 thick tufted 1 and 2”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Morphology classification
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In the paper
“clustering them together resulted in a similar, though not identical, number of clusters (14 total), but it also produced one cluster that contained both excitatory and inhibitory neurons”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
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It may state two separate claims as one.
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In the paper
“The excitatory e-types were relatively similar to each other, with wide APs and similar distributions of membrane capacitance and input resistance”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
plain- 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
“Inhibitory me-types were consistent with the different inhibitory e-types, although there was some mixing between, for example, the different fast-spiking e-types (Inh_8 through Inh_13”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Joint classification with electrophysiology and morphology
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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
“This procedure yielded 17 total clusters, or e-types: four e-types for the 928 excitatory neurons and thirteen for the 1,010 inhibitory neurons.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- The authors state this as an assumption: Spiny neurons are excitatory.
- The authors state this as an assumption: Aspiny or sparsely spiny neurons are inhibitory.
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
“On the inhibitory side, e-types showed relatively high consistency, m-types had lower scores, and most me-types were again highly consistent with transcriptomic subclasses—for many me-types, a single subclass had a high score while the rest were low”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Joint classification with electrophysiology and morphology
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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
“Spiny m-types were predominantly found in a single layer, but were not exclusive to that layer, although see Spiny_1, 3, 10, 14, and 19”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Morphology classification
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In the paper
“The 19 m-types for inhibitory interneurons were distributed across all cortical layers (L1-L6b), with most m-types found in multiple layers with the exception of several L2/3-specific m-types”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Morphology classification
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In the paper
“Each of these me-types was usually consistent with an excitatory m-type (Fig. 5c), though in some cases multiple m-types were collapsed into fewer me-types.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Joint classification with electrophysiology and morphology
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“membrane capacitance values were nearly all lower than those of the excitatory e-types (though Inh_4 was a notable exception)”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
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
“The distribution of m-types varied across transgenic lines (Supplementary Fig. 22), and many, but not all, m-types were found in relatively consistent locations on the electrophysiology-based t-SNE projection”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Morphology classification
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In the paper
“Relative soma depth, dendrite and axon size and distribution were all important for distinguishing among inhibitory m-types”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Morphology classification
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In total, 38 clusters or m-types were identified, 19 for spiny neurons (Fig. 3) and 19 for aspiny neurons (Fig. 4).”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Morphology classification
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
“All but 9 of those 461 cells underwent electrophysiological classification; the primary reason for not including these nine was failure to elicit an action potential with the 25 pA/s ramp stimulus.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Creating the in vitro single cell characterization platform
plaindirect- 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
“Aspiny m-types within a subclass (e.g., nest and small BCs) were frequently merged within a layer, but we also identified fairly distinct groupings of Martinotti cells, double-bouquet cells, and chandelier cells”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Morphology classification
plain- 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
“here certain e-types had higher proportions of neurons that exhibited these patterns (e.g., Exc_4 for bursting, Inh_1 for delayed firing) but were not strictly demarcated by these patterns.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
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
“Among excitatory cells, we found that most excitatory e-types had low consistency scores (except Exc_4), while more m-types had higher scores, and even more me-types had high scores”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Joint classification with electrophysiology and morphology
plaincorrelational- 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.
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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
“Of these, 928 were spiny neurons, which we assume to be excitatory, and 1,010 were aspiny or sparsely spiny, which we assume to be inhibitory”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Creating the in vitro single cell characterization platform
plain- 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.
- The authors state this as an assumption: Spiny neurons are excitatory.
- The authors state this as an assumption: Aspiny or sparsely spiny neurons are inhibitory.
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
“Pvalb-labeled cells were adjacent to Sst cells, and Vip cells were found on the other side of Sst cells.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This led to the identification of 17 e-, 38 m-, and 46 me-types”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
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In the paper
“For example, we identify 46 me-types by joint clustering, in contrast to the 120 observed combinations by just intersecting e- and m-types (Supplementary Fig. 29).”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
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In the paper
“Interestingly, Penk-IRES2-Cre-neo in L5-L6 and Oxtr-T2A-Cre in L6, which labeled overlapping sets of t-types, both identified the same me-type (ME_Exc_6)”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Correspondence with specific transcriptomic types
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Analysis of inhibitory neurons yielded 56 total components, excitatory neurons yielded 54 components, and all neurons combined yielded 54 components.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Electrophysiological classification.
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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.
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In the paper
“The L5-L6 neurons labeled by a Nos1/Sst intersectional strategy were quite coherent in the electrophysiological t-SNE projection and had mostly one of two similar me-types”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Correspondence with specific transcriptomic types
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In the paper
“However, other combinations labeling between one and three t-types predominantly had a single me-type (Fig. 7b-d), which were also tightly clustered in the electrophysiological t-SNE projection.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Correspondence with specific transcriptomic types
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In the paper
“Accordingly, we found that these neurons had me-types that contained fast-spiking cells and had basket-cell and chandelier-cell morphologies (see Figs. 5d and 6b).”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Correspondence with specific transcriptomic types
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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
“This mouse morpho-electric visual cortical dataset is large and diverse”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
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In the paper
“This emphasized the “sag” in the membrane potential due to the activation of Ih observed in some cells.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Electrophysiological feature analysis.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Random forest classifier gave 79/70% out-of-bag prediction accuracy and support vector machine showed 89/79% prediction accuracy in leave-one-out cross validation for spiny/aspiny neurons.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Morphology feature design and clustering.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The dendritic morphology of each neuron (N=1938) was identified as either aspiny, sparsely spiny or spiny49 based on a qualitative assessment of the neuron’s dendrites by viewing the slides under the microscope and/or in the 63X image.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Dendrite type assignment.
What the sources say
- Not checked yetcites [49] Tripathy, S. J. et al. Transcriptomic correlates of neuron electrophysiological diversity. PLoS Comput. Biol. 13, e1005814 (2017). source
plainn = 1,938- Asserted: passes — The authors put it forward as true.
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In the paper
“Specific cell types have been characterized quantitatively9–11, but these studies frequently have used additional labels (individual gene markers) to pre-define cell types.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
What the sources say
- Not checked yetcites [9] Bortone, D. S., Olsen, S. R. & Scanziani, M. Translaminar inhibitory cells recruited by layer 6 corticothalamic neurons suppress visual cortex. Neuron 82, 474–485 (2014). source
- Not checked yetcites [10] Kim, E. J., Juavinett, A. L., Kyubwa, E. M., Jacobs, M. W. & Callaway, E. M. Three types of cortical layer 5 neurons that differ in brain-wide connectivity and function. Neuron 88, 1253–1267 (2015). source
- Not checked yetcites [11] Dehorter, N. et al. Tuning of fast-spiking interneuron properties by an activity-dependent transcriptional switch. Science 349, 1216–1220 (2015). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“A diverse set of transgenic mouse lines14–18 were used to ensure broad coverage of excitatory and inhibitory classes across all cortical layers, to enable selective targeting of rare cell populations, and to link our study with other experimental approaches, such as transcriptomic characterization19.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
What the sources say
- Not checked yetcites [14] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source
- Not checked yetcites [15] Peng, H., Ruan, Z., Long, F., Simpson, J. H. & Myers, E. W. V3D enables real-time 3D visualization and quantitative analysis of large-scale biological image data sets. Nat. Biotechnol. 28, 348–353 (2010). source
- Not checked yetcites [16] Harris, J. A. et al. Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation. Front. Neural Circuits 8, 76 (2014). source
- Not checked yetcites [17] Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140 (2010). source
- Not checked yetcites [18] Daigle, T. L. et al. A suite of transgenic driver and reporter mouse lines with enhanced brain-cell-type targeting and functionality. Cell 174, 465–480.e22 (2018). source
- Not checked yetcites [19] Bernard, A., Sorensen, S. A. & Lein, E. S. Shifting the paradigm: new approaches for characterizing and classifying neurons. Curr. Opin. Neurobiol. 19, 530–536 (2009). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“excitatory neuron populations with features often linked to their laminar locations as well as the locations to which they project their axons2–4”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
What the sources say
- Not checked yetcites [2] 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 [3] Harris, K. D. & Shepherd, G. M. G. The neocortical circuit: themes and variations. Nat. Neurosci. 18, 170–181 (2015). source
- Not checked yetcites [4] Lodato, S. & Arlotta, P. Generating neuronal diversity in the mammalian cerebral cortex. Annu. Rev. Cell Dev. Biol. 31, 699–720 (2015). source
plaincorrelational- 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
“Every aspect of the pipeline, from slice preparation, recording, and stimulation, to staining, imaging, reconstruction, and mapping of cells to a reference atlas, employed highly standardized and quality-controlled methodology.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“these approaches may successfully identify heterogeneity in features between specific populations under investigation, but these differences may not necessarily co-vary with other features or display discontinuities when examined in the context of a broader set of cortical cells—significant criteria for cell-type classification1.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
What the sources say
- Not checked yetcites [1] Zeng, H. & Sanes, J. R. Neuronal cell-type classification: challenges, opportunities and the path forward. Nat. Rev. Neurosci. 18, 530–546 (2017). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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
“features used to distinguish types can be specific to the population being studied and may not be broadly applicable (or distinguishing) across all cortical neurons.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
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. 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
“We characterized mouse visual cortex neurons with a uniform experimental protocol and developed an unsupervised classification scheme of cell types based on electrophysiology and morphology.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Such qualitative descriptions are valuable and can be consistent with statistical analyses of features8, but they can be limited by the number of criteria that can be simultaneously used to differentiate types.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
What the sources say
- Not checked yetcites [8] Druckmann, S., Hill, S., Schürmann, F., Markram, H. & Segev, I. A hierarchical structure of cortical interneuron electrical diversity revealed by automated statistical analysis. Cereb. Cortex 23, 2994–3006 (2013). source
plainconditional- 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
“Recent studies using transcriptomic characterization based on single-cell RNA-sequencing techniques performed unsupervised classification to generate a taxonomy of transcriptomic types in the mouse neocortex12–14.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
What the sources say
- Not checked yetcites [12] Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016). source
- Not checked yetcites [13] Zeisel, A. et al. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347, 1138–1142 (2015). source
- Not checked yetcites [14] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source
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
“Recent studies performed at larger scales5,6, including the Blue Brain Project’s thorough classification of morpho-electric diversity in juvenile rat somatosensory cortex, have overcome many of these issues, using large, coherent data sets to identify principles of local connectivity and computation within a cortical column.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
What the sources say
- Not checked yetcites [5] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462 (2015). source
- Not checked yetcites [6] Markram, H. et al. Reconstruction and simulation of neocortical microcircuitry. Cell 163, 456–492 (2015). source
plaindirect- 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 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
“These approaches rely on data from thousands of neurons generated in a standardized manner.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
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.
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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
“leading to the characterization of three major populations (i.e., Pvalb+, Sst+, and Htr3a+) of neocortical interneurons, each with distinct types”
§ Classification of electrophysiological and morphological types in mouse visual cortex > INTRODUCTION
What the sources say
- Not checked yetcites [2] 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 [3] Harris, K. D. & Shepherd, G. M. G. The neocortical circuit: themes and variations. Nat. Neurosci. 18, 170–181 (2015). source
- Not checked yetcites [4] Lodato, S. & Arlotta, P. Generating neuronal diversity in the mammalian cerebral cortex. Annu. Rev. Cell Dev. Biol. 31, 699–720 (2015). source
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
“This agrees with previous descriptions of excitatory m-type distribution in other brain regions8,21.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Morphology classification
What the sources say
- Not checked yetcites [8] Druckmann, S., Hill, S., Schürmann, F., Markram, H. & Segev, I. A hierarchical structure of cortical interneuron electrical diversity revealed by automated statistical analysis. Cereb. Cortex 23, 2994–3006 (2013). source
- Not checked yetcites [21] Baden, T. et al. The functional diversity of retinal ganglion cells in the mouse. Nature 529, 345–350 (2016). source
plaincorrelational- 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
“All recorded cells underwent the same workflow (Fig. 1a), and only cells that met pre-defined quality control (QC) standards were included in the final data set, which consisted of 1,938 cells passing electrophysiology QC.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Creating the in vitro single cell characterization platform
plain- 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.
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
“We characterized the intrinsic electrophysiological properties with a standardized current-clamp protocol that contained a variety of stimuli, including square pulses, ramps, and noisy current injections”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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
“Properties may vary considerably within a type as long as gradual variation is present; the existence of these intermediates means that there is no identifiable place to subdivide the cluster.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
hedgeddirect- Asserted: passes — The authors put it forward as true.
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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
“This cohesiveness suggests that there is similarity in e-features within genetically-defined populations of cortical cells, as well as distinctiveness between non-overlapping populations.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > RESULTS > Electrophysiology classification
hedgedcorrelational- 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
“Image quality control included a z-stack plane count, a visual check for proper stitching alignment and even illumination throughout the images. 63X Z-stacks were evaluated based on quality metrics that would impact cell reconstruction, as opposed to aesthetic quality.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Imaging.
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.
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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.
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
“Our approach, while certainly not free of biases (e.g., choice of stimuli delivered to the cells, morphological features quantified), has the advantage of being quantitative, reproducible, transferable to new data (e.g., Supplementary Fig. 24-26), and robust across the varied characteristics of the entire population of neurons studied.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
plain- 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
“Our methods and data are publicly accessible as part of the Allen Cell Types Database at celltypes.brain-map.org”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
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
“we used both electrophysiological and morphological features measured from the same cell together when possible.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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
“Electrophysiologically, truncated neurons were distributed in each type and found throughout the t-SNE representation of electrophysiology space.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Tissue processing.
plain- 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.
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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
“The entire procedure (including the robustness evaluation) was repeated on 90% subsets of the dataset to generate a cellwise co-clustering matrix, which supported the assessment of cluster stability.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Electrophysiological classification.
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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
“However, Exc_4 has the lowest fraction of neurons with a truncated apical dendrite, and the region of the t-SNE projection where Exc_4 is primarily represented appears to have fewer truncated neurons (Supplementary Fig. 32).”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Tissue processing.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The recent finding of shared t-types among inhibitory cells but different t-types among excitatory cells from separate cortical areas14”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
What the sources say
- Not checked yetcites [14] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source
plaincorrelational- 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. 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
“Although only spiny neurons with an intact apical dendrite were included in morphological analysis, all neurons were included in electrophysiology analysis, though the truncation of the apical dendrite was annotated.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Tissue processing.
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. 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
“Image quality evaluation included a qualitative evaluation of signal to noise for the imaged object (with high signal apparent in the cell body and dendrites, as opposed to background stain in the surrounding tissue, which can occur when cell filling leaks), in-focus cell body, and absent or negligible tessellation (tiling and stitching edge artifact). Overall evenness of section illumination and”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Imaging.
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. 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
“we note that our electrophysiological results reflect the specific experimental protocols used here”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
plaindirect- 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
“All procedures were carried out in accordance with Institutional Animal Care and Use Committee at the Allen Institute for Brain Science.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Mouse breeding and husbandry
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.
In the paper
“It is known that individual t-types can exhibit substantial continuous variation within a type14”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
What the sources say
- Not checked yetcites [14] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source
boosted- 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.
In the paper
“Cluster stability was then evaluated by subsampling analysis23.”
- Also stated in: § Electrophysiological classification. · plain
“clusters that had average Jaccard similarities below 0.5 were dissolved by merging into other clusters (using the entropy criterion above), resulting in a final set of clusters, or e-types.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Electrophysiological classification.
What the sources say
- Not checked yetcites [23] Hennig, C. Cluster-wise assessment of cluster stability. Comput. Stat. Data Anal. 52, 258–271 (2007). 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.
Probably not a substantial claim. It may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Electrophysiological classification. · 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
“To be included in analysis, a > 1 GΩ seal was recorded prior to break-in and the initial access resistance < 20 MΩ and < 15% of the Rinput.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Patch clamp recording.
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.
Probably not a substantial claim. 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
“The composition of bath and internal solution as well as preparation methods were made to a) maximize the tissue quality of slices from adult mice, and b) align with solution compositions typically used in the field (to maximize the chance of comparison to previous studies).”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Patch clamp recording.
plaindirect- 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.
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
“For an individual sweep to be included: (1) the bridge balance was < 20 MΩ and < 15% of the Rinput, (2) bias (leak) current 0 +/- 100 pA”
- Also stated in: § Patch clamp recording. · plain
“(3) root mean square (RMS) noise measurements in a short window (1.5 ms, to gauge high frequency noise) and longer window (500 ms, to measure patch instability) < 0.07 mV and 0.5 mV, respectively and (4) the difference in the voltage at the end of the data sweep (measured over 500 ms of rest) and the voltage measured immediately prior to the stimulus onset < 1 mV.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Patch clamp recording.
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.
Probably not a substantial claim. It may state two separate claims as one.
- Also stated in: § Patch clamp recording. · 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
“Data from putatively excitatory cells and inhibitory cells (determined by the presence and type of dendritic spines) were analyzed separately, though similar results were observed when all cells were analyzed together (see Supplementary Fig. 6).”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Electrophysiological classification.
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.
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
“suggests that applying the methods of this study to a different cortical area may identify the same inhibitory me-types.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
hedgedconditional- 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
“In addition, the procedure was used on 20%, 40%, 60%, and 80% random subsamples of the data (each drawn 10 times) to evaluate how the number of clusters identified varied with the number of samples used in the analysis.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Electrophysiological classification.
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.
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 code for feature analysis is publicly available as part of the Allen SDK.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Electrophysiological feature analysis.
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
“direct comparisons with previous studies should take into account the fact that specific protocols and solution composition vary within the literature.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Patch clamp recording.
plain- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Large-scale transcriptomic studies have provided informative taxonomies of cortical cell types12–14.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > DISCUSSION
What the sources say
- Not checked yetcites [12] Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016). source
- Not checked yetcites [13] Zeisel, A. et al. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347, 1138–1142 (2015). source
- Not checked yetcites [14] Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72–78 (2018). source
plaindirect- 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.
Probably not a substantial claim.
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
“Clusters with average Jaccard similarities of below 0.5 were considered unstable and were merged with another cluster with the highest between-cluster rate if it exceeded 35% (chosen because it was similar to the 5th percentile of the within-cluster rates of all cells in stable clusters).”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Joint electrophysiological and morphological clustering.
plaindirect- 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.
Probably not a substantial claim. 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
“As a final step in the manual correction and curation process, an alternate analyst checked for missed branches or inappropriate connections.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Morphological reconstruction.
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 different stimulus protocols were not presented in a randomized order.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Statistics and research design.
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
“Data collection and analysis were not performed blind to the conditions of the experiments as there was a single experimental condition for all acquired data.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Statistics and research design.
plaindirect- 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.
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 randomization was used during data collection as there was a single experimental condition for all acquired data.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Statistics and research design.
plaindirect- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Automated reconstructions were then extensively manually corrected and curated using a range of tools (e.g., virtual finger, polyline) in the Mozak extension (Zoran Popovic, Center for Game Science, University of Washington) of Terafly tools50,53 in Vaa3D.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Morphological reconstruction.
What the sources say
- Not checked yetcites [50] Neher, E. Correction for liquid junction potentials in patch clamp experiments. Methods Enzymol. 207, 123–131 (1992). source
- Not checked yetcites [53] Peng, H., Bria, A., Zhou, Z., Iannello, G. & Long, F. Extensible visualization and analysis for multidimensional images using Vaa3D. Nat. Protoc. 9, 193–208 (2014). source
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
“However, to test the effects of z-shrinkage and tilt angle on the classification results, we restored reconstructions to their original volumes and aligned them to the perpendicular cortical axis (based on registration to the common mouse reference atlas), and re-ran our clustering analysis (Supplementary Fig. 33). We found good agreement between the clustering results before and after adjustment.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Morphology feature design and clustering.
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.
None of the sources cited for this claim have been checked yet.
In the paper
“No statistical methods were used to pre-determine sample sizes, but the sample sizes here are similar to those reported in previous publications5,6,12.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Statistics and research design.
What the sources say
- Not checked yetcites [5] Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462 (2015). source
- Not checked yetcites [6] Markram, H. et al. Reconstruction and simulation of neocortical microcircuitry. Cell 163, 456–492 (2015). source
- Not checked yetcites [12] Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016). source
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. 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
“The p-values were adjusted for multiple testing using the two-stage Benjamini and Hochberge step-up procedure to control the false discovery rate.”
§ Classification of electrophysiological and morphological types in mouse visual cortex > METHODS > Statistics and research design.
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.
Probably not a substantial claim.
- The authors state this as an assumption: Morphological feature distributions were assumed to be normal for the t-test, but this was not formally tested.
The authors state this as an assumption.
Spiny neurons are excitatory.
“928 were spiny neurons, which we assume to be excitatory”
The authors state this as an assumption.
Aspiny or sparsely spiny neurons are inhibitory.
“1,010 were aspiny or sparsely spiny, which we assume to be inhibitory”
The paper relies on this without support.
Smaller studies could not be directly compared for morpho-electric properties because of differing protocols, analysis methods, and transgenic line availability, which hindered building a systematic classification.
“Historically, though, direct comparisons of morpho-electric properties across smaller studies have been constrained by differences in experimental protocols, analysis methods, and access to specific transgenic lines, limiting the construction of a systematic classification scheme.”
The paper relies on this without support.
The features that separate types may be particular to the studied population and may not generalize to all cortical neurons.
“features used to distinguish types can be specific to the population being studied and may not be broadly applicable (or distinguishing) across all cortical neurons.”
The authors state this as an assumption.
Sncg inhibitory subclass cells are underrepresented in the dataset.
“we presume that these cells are underrepresented in our data set”
The paper relies on this without support.
Transgenic lines are imperfect labels of transcriptomic cell types.
“While transgenic lines are imperfect labels of transcriptomic cell types”
The authors state this as an assumption.
Morphological feature distributions were assumed to be normal for the t-test, but this was not formally tested.
“Morphological feature distributions were assumed to be normal for this method, but this was not formally tested (see Supplementary Figs. 19 and 21 for plots of distributions).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Electrophysiological features were measured from responses elicited by short (3 ms) current pulses and long (1 s) current steps as previously described (Gouwens et al., 2019).”
From Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells (2020) · cites this paper as Gouwens et al., 2019
In the citing paper
“The observed phenotypes included most of the morphological and electrophysiological types of cortical neurons that have been described previously in mice and rats5,6,24, allowing us to link transcriptomic and morpho-electric descriptions (Extended Data Fig. 3, Supplementary File 1).”
From Phenotypic variation of transcriptomic cell types in mouse motor cortex (2021) · cites this paper as [24]
In the citing paper
“Previous studies using transgenic lines had shown that morpho-electric properties within these families can be highly variable5,24.”
From Phenotypic variation of transcriptomic cell types in mouse motor cortex (2021) · cites this paper as [24]
In the citing paper
“the number of VISp GABAergic “t-types” (60) and “me-types” (26) - differs by more than a factor of two”
From Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells (2020) · cites this paper as Gouwens et al., 2019
In the citing paper
“This is in qualitative agreement with the findings of Gowens et al.76, who, in a parallel work based on unsupervised clustering, identified twice as many morphological types (m-types) as electrophysiological ones (e-types).”
From Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas (2019) · cites this paper as [76]
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Metadata
- Authors
- Gouwens, N. W., Sorensen, S. A., Berg, J., Lee, C., Jarsky, T., Ting, J., Sunkin, S. M., Feng, D., Anastassiou, C. A., Barkan, E., Bickley, K., Blesie, N., Braun, T., Brouner, K., Budzillo, A., Caldejon, S., Casper, T., Castelli, D., Chong, P., Crichton, K., Cuhaciyan, C., Daigle, T. L., Dalley, R., Dee, N., Desta, T., Ding, S.-L., Dingman, S., Doperalski, A., Dotson, N., Egdorf, T., Fisher, M., de Frates, R. A., Garren, E., Garwood, M., Gary, A., Gaudreault, N., Godfrey, K., Gorham, M., Gu, H., Habel, C., Hadley, K., Harrington, J., Harris, J. A., Henry, A., Hill, D., Josephsen, S., Kebede, S., Kim, L., Kroll, M., Lee, B., Lemon, T., Link, K. E., Liu, X., Long, B., Mann, R., McGraw, M., Mihalas, S., Mukora, A., Murphy, G. J., Ng, L., Ngo, K., Nguyen, T. N., Nicovich, P. R., Oldre, A., Park, D., Parry, S., Perkins, J., Potekhina, L., Reid, D., Robertson, M., Sandman, D., Schroedter, M., Slaughterbeck, C., Soler-Llavina, G., Sulc, J., Szafer, A., Tasic, B., Taskin, N., Teeter, C., Thatra, N., Tung, H., Wakeman, W., Williams, G., Young, R., Zhou, Z., Farrell, C., Peng, H., Hawrylycz, M. J., Lein, E., Ng, L., Arkhipov, A., Bernard, A., Phillips, J. W., Zeng, H., & Koch, C.
- Affiliations
- Allen Institute for Brain Science (US)
- Corresponding author
- Zeng, Hongkui
- ORCID
- Gouwens, Nathan W.
- Sorensen, Staci A.
- Berg, Jim
- Lee, Changkyu
- Jarsky, Tim
- Ting, Jonathan
- Sunkin, Susan M.
- Feng, David
- Anastassiou, Costas A.
- Barkan, Eliza
- Bickley, Kris
- Braun, Thomas
- Brouner, Krissy
- Budzillo, Agata
- Caldejon, Shiella
- Casper, Tamara
- Chong, Peter
- Crichton, Kirsten
- Daigle, Tanya L.
- Dalley, Rachel
- Dee, Nick
- Desta, Tsega
- Ding, Song-Lin
- Dotson, Nadezhda
- Egdorf, Tom
- Fisher, Michael
- Gary, Amanda
- Gorham, Melissa
- Hadley, Kristen
- Harris, Julie A.
- Henry, Alex
- Hill, DiJon
- Kebede, Sara
- Kim, Lisa
- Kroll, Matthew
- Lee, Brian
- Link, Katherine E.
- Liu, Xiaoxiao
- Long, Brian
- Mann, Rusty
- Mihalas, Stefan
- Mukora, Alice
- Murphy, Gabe J.
- Ng, Lindsay
- Nguyen, Thuc Nghi
- Nicovich, Philip R.
- Oldre, Aaron
- Potekhina, Lydia
- Reid, David
- Schroedter, Martin
- Slaughterbeck, Cliff
- Soler-Llavina, Gilberto
- Szafer, Aaron
- Tasic, Bosiljka
- Taskin, Naz
- Teeter, Corinne
- Tung, Herman
- Wakeman, Wayne
- Williams, Grace
- Zhou, Zhi
- Farrell, Colin
- Hawrylycz, Michael J.
- Lein, Ed
- Ng, Lydia
- Arkhipov, Anton
- Bernard, Amy
- Phillips, John W.
- Zeng, Hongkui
- Koch, Christof
- Venue
- Nature Neuroscience
- Published
- 2019-06-17
- Volume
- 22
- Issue
- 7
- Pages
- 1182-1195
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC8078853
- OpenAlex
- W2949311293
- Semantic Scholar
- fccd157b961e9e3bfa5a0d5616b3a3ecb381ce85
- Cited by
- 456
- References
- 59
- Citations by year
- 2026: 44 · 2025: 69 · 2024: 54 · 2023: 64 · 2022: 63 · 2021: 66 · 2020: 62 · 2019: 30
- FWCI
- 26.25
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Neuroscience (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (U01MH105982, U19MH114830)
- National Eye Institute (R01EY023173)
- 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
- neuron classification, mouse visual cortex, neuronal morphology, electrophysiological properties, single-cell characterization, unsupervised clustering
- MeSH terms
- Action Potentials, Animals, Mice, Transgenic, Neurons, Visual Cortex, Databases, Factual, Genes, Reporter, Patch-Clamp Techniques, Cell Shape, Mice, Transcriptome, Datasets as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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