Sensory inputs control the integration of neurogliaform interneurons into cortical circuits

De Marco García, Priya, Tuncdemir, Fishell, Karayannis · Nature Neuroscience · 2015 · neuroscience · 10.1038/nn.3946 · record De-Marco-Garc-a2015-sensory-inputs-control-the-integration-of-ne
tag layer · index · concepts · authors · עברית
Where this record's text came from. faceted 2026-08 by reading the locally held text (xml); every evidence string verified as an exact substring of that text before merging. The method vocabulary has no term for the paper's core techniques (monosynaptic rabies tracing, in utero electroporation, conditional knockouts, ChR2 optogenetic mapping); electrophysiology was chosen because whole-cell recording is the method the paper uses to establish its functional claims, and the method quote is explicit about it. Prior work in claim relations is cited only by superscript number in this text, so targets are described rather than named. The finding that VIP+ interneurons are unaffected is a within-paper negative control rather than a separate null-result claim, so claim type stays mechanism. 2026-08-13 and 2026-08-15 schema-0.3 passes: every quote verified as an exact substring of the staged text and anchored at merge time; concept terms verified present; every edge endpoint an existing node.
How to read this page. The article itself is not reproduced here — this paper is not cleared for redistribution, so what follows is the tag layer alone. The evidence sentences are withheld with the article. The table at the foot lists every tag the record carries; each row names the facet it belongs to, and the whose words column says whether the tag records the paper's own wording or the tagger's sentence about the paper. Every tag links to each other paper in the corpus carrying it. The machine-readable edition of the same thing is the TEI file beside this one, where the tags live in standOff, and the article is at its publisher via the link below. When we have changed our mind. Some entries in the table begin with a word in capitals and the reason for it. EVIDENCE CORRECTED — the finding still stands, but we had quoted the wrong sentence from the paper, and the quotation has been replaced with the right one. RETRACTED — the entry itself was wrong; it stays on the page, marked, with the reason, rather than being deleted. WITHDRAWN AND REPLACED — the entry was wrong, and a corrected version of it appears in the entries below. Each mark carries its own reason, in brackets, because the reasons differ from one entry to the next. An entry we have WITHDRAWN is removed from this page and kept in the record, with its reason. A line reading Audit and a date is a later re-reading of the entry against its whole sentence: DOUBTFUL means it was kept, and the reason says what is loose about it. Quotation marks inside the tagger's sentence. Where a tag is the tagger's own sentence, a phrase in quotation marks inside it is borrowed from the paper — the tagger's wording around it is not. The paper's own sentence is the evidence quote for that row; on this page it is withheld with the article, and the article is at its publisher. Nothing inside quotation marks anywhere on this page is ours: if it is quoted, it is the paper's. Whose words a concept carries. A concept entry records a term the paper itself uses, so the term, the sense given for it, and its evidence are the paper's own words, quoted where the paper fixes them. This is the opposite of a sense entry in the tag table, which is the tagger's sentence about how the paper uses a term. Where a concept entry could not be grounded in the paper's words, the entry says so on its own row.

Tags on this paper

Every tag the record carries, each linking to every other paper in the corpus that carries it. A tag appears here whether or not its words occur in the article — the spans below are only the ones a sentence in this paper licenses. Of the 14 concept tags on this paper, none is grounded in a quoted sentence. All carry the tagger's gloss of what the term means in this paper, which is not something the article can license.
neurogliaform Reelin VIP thalamic intracortical NMDA NR2B NR2A AMPAR monosynaptic rabies tracing starter cell whisker plucking nucleus basalis critical period Developing interneurons discriminate between otherwise similar glutamatergic afferents according to which postsynaptic receptor subtype those afferents engage NR2B-containing NMDA receptors are preferentially allocated to the dendritic postsynaptic sites that receive thalamic input, giving ascending afferents a privileged signalling channel NMDA receptor activation drives the interneuron's integration into the nascent circuit, so that losing it both stunts the arbor and shifts the balance of afferents toward local cortical sources interneuron rabies whisker somatosensory monosynaptic electroporation channelrhodopsin barrel VAMP2 chronic bilateral whisker plucking genetic blockade thalamic afferent connectivity intracortical pyramidal cell innervation dendritic length complexity of axonal arbors Mann-Whitney U test Mann-Whitney test t-test unpaired t -test standard error of the mean p-value unpaired t-test on morphological measures proportion of presynaptic partners by source electrophysiology

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second readingalternativesan independent re-reading of a facet, recorded whether or not it agrees
relation to other workclaim_relationshow this paper stands to another: agrees, contradicts, extends, qualifies
claim typeclaim_typethe shape of the claim: existence, mechanism, method, critique, prediction, null
concept edgeconcept_edgesan asserted relation between two concepts, with the sentence asserting it
content tagcontent_tagsa finding, definition, quantity, statistic or variable named in the paper
contributioncontributionwhat the paper claims to add
controlcontrolsan experiment run to eliminate a rival explanation
limitationlimitationswhat the paper says its evidence cannot support
mechanismmechanismshow the reported effect is said to come about
methodmethodhow the paper produced its evidence
object of studyobject_of_studywhat the paper is about — the thing it investigates
phenomenonphenomenonthe effect or regularity under study
research questionresearch_questionthe question the paper sets itself
sensesensesa distinct use of a term, quoted where the paper fixes it
transfertransfersa method or concept carried in from another field

The paper

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Every tag on this page

alternatives 3 · claim_relations 6 · claim_type 1 · concept_edges 5 · content_tags 42 · contribution 1 · controls 1 · limitations 6 · mechanisms 9 · method 1 · object_of_study 1 · phenomenon 1 · research_question 1 · senses 4 · transfers 2

Relations on this page carry a quotation for the claim. Where a relation was separately evidenced — and so tested against the vocabulary for its type — the row says so; none of 5 relations here carry that mark. The rest are the tagger’s reading of the sentence quoted beside them.

facettagfieldconf.whose words
object_of_studyhow Reelin-expressing neurogliaform interneurons acquire their pattern of afferent connectivity during the first postnatal week
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object_of_studythe paper's words
research_questionwhat regulates the balance between thalamic and intracortical inputs onto developing superficial interneurons
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research_questionthe paper's words
contributionshows superficial Reelin interneurons receive direct thalamic input during development, and that NMDA receptor signalling through it sets the ratio of thalamic to intracortical connectivity
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contributionthe paper's words
claim_typemechanism
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claim_typethe paper's words
phenomenoncortical interneuron circuit integration
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phenomenonthe paper's words
methodelectrophysiology
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methodthe paper's words
mechanismsmechanisms
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mechanisms[0]the tagger's words
mechanismsmechanisms
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mechanisms[1]the tagger's words
mechanismsmechanisms
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mechanisms[2]the tagger's words
mechanismssparse electroporation plus focal rabies injection yields one starter cell per brain, so the traced inputs belong to a single identified interneuron
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mechanisms[3]1.0the tagger's words
mechanismsanatomical tracing is confirmed functionally by optogenetic mapping with TTX and 4AP, isolating monosynaptic responses
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mechanisms[4]1.0the tagger's words
mechanismsthe requirement is timed: removing the receptor at P3 reproduces the defect and at P6 does not, placing the critical window between them
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mechanisms[5]1.0the tagger's words
mechanismsthe effect is subunit-specific - NR2B-containing receptors are required, NR2A-containing ones are not
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mechanisms[6]1.0the tagger's words
mechanismsAMPA receptor signalling remains intact and is not sufficient: the cells still fail to develop axons or integrate
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mechanisms[7]1.0the tagger's words
mechanismsthe total input count is preserved while its composition flips, so this is reallocation rather than loss
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mechanisms[8]1.0the tagger's words
limitationsThe authors could not rule out that some cortical glutamatergic signalling survived their viral tetanus-toxin blockade of intracortical input.
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what this limits: the completeness of the silencing: WE COULD NOT FORMALLY EXCLUDE THE POSSIBILITY THAT RESIDUAL CORTICAL GLUTAMATERGIC SIGNALING TO Re+ INTERNEURONS PERSISTED
limitations[0]the tagger's words
limitationsThe complete-intracortical-blockade genotype yielded very few animals, so a second mouse line had to be generated to enlarge the sample.
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what this limits: the complete-blockade analysis: IN AN EFFORT TO INCREASE THE SAMPLE SIZE FOR THIS ANALYSIS, WE GENERATED MICE containing a second allele combination, because the first genotype was too rare
limitations[1]the tagger's words
limitationsthe absence of neuromodulatory input is overridden by inference from the authors' own prior work, which says it must appear eventually
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what this limits: the claim that these cells lack neuromodulatory input: WE DID NOT OBSERVE APPRECIABLE INPUTS ... FROM ASCENDING NEUROMODULATORY FIBERS, supported by SUPPLEMENTARY FIG. 3 AND DATA NOT SHOWN
limitations[2]1.0the tagger's words
limitationsinterneuron-to-interneuron connectivity did not change significantly, with only three mutant animals
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what this limits: the interneuron-to-interneuron connectivity comparison: NOT SIGNIFICANTLY CHANGED (CTRL: 27% +/- 6 VERSUS 42% +/- 4, P = 0.103) - a null on a small sample rather than an established absence
limitations[3]1.0the tagger's words
limitationsthe cross-species claim about the proportion of these interneurons is explicitly a speculation
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what this limits: the cross-species reading: Quotation withheld
limitations[4]1.0the tagger's words
limitationswhether VIP interneurons use intrinsic programs or unidentified activity sources is left open
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what this limits: the generality of the activity-dependence claim: VIP+ INTERNEURONS MAY USE EITHER INTRINSIC GENETIC PROGRAMS OR AS-YET-UNIDENTIFIED SOURCES OF ACTIVITY
limitations[5]1.0the tagger's words
transfersmonosynaptic rabies tracing, adapted to single starter cells and to developmental time points
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transfers[0]1.0the tagger's words
transfersthe finding that specific rather than global activity refines connectivity, used as the frame for this result
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transfers[1]0.8the tagger's words
controlsthe same rabies-tracing experiment repeated in a LARGER AND DIFFERENT SUBSET of superficial interneurons, including VIP- and calretinin-expressing subtypes
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eliminates: a bias in the method itself - if rabies tracing simply fails to label some synapse types, the absence of nucleus basalis input onto Re+ interneurons would be an artefact of the tracer rather than a fact about the circuit · outcome: held
controls[0]0.95the tagger's words
sensesbalance here is a RATIO of afferent sources whose total is conserved - thalamic falls from 60% to 16% while intracortical rises from 14% to 42%, with the same number of presynaptic cells
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senses[0]1.0the tagger's words
sensesthe same glutamatergic input is distinguished not by its transmitter but by which postsynaptic receptor it acts on, which is what lets one afferent source matter and another not
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senses[1]1.0the tagger's words
sensesRe-positive and VIP-positive interneurons are used throughout as a built-in contrast: every manipulation that impairs one leaves the other intact
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senses[2]1.0the tagger's words
sensesthe absence of cholinergic input is scoped to this age, not to this cell type - the authors expect it to appear later
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senses[3]1.0the tagger's words
alternativesclaim_type: mechanism
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a second reading reaching the same value. Recorded: mechanism — note: a second reading reaching the same value from a different sentence. Not applied - a person decides.
alternatives.claim_typethe tagger's words
alternativesmethod: monosynaptic rabies tracing from single starter interneurons, ChR2-assisted circuit mapping, whisker deprivation, and cell-autonomous conditional removal of NMDA receptor subunits
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a second reading DIFFERING from the recorded value. Recorded: electrophysiology — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides.
alternatives.methodthe tagger's words
alternativesphenomenon: activity-dependent assembly of cortical microcircuits
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a second reading DIFFERING from the recorded value. Recorded: cortical interneuron circuit integration — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides.
alternatives.phenomenonthe tagger's words
claim_relationsextends → previous work showing that sensory experience shapes the topography of the sensory cortices (refs 33-37)
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claim_relations[0]the tagger's words
claim_relationsbuilds-on → the authors' own preceding study of how dampened excitation affects interneuron positioning and maturation (ref 9)
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claim_relations[1]the tagger's words
claim_relationscontradicts → the classical view that layer IV is the primary recipient of ascending thalamic sensory input
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claim_relations[2]1.0the tagger's words
claim_relationsextends → the authors' own earlier finding that Re-positive but not VIP-positive interneurons require activity to mature
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claim_relations[3]1.0the tagger's words
claim_relationssupports → retinogeniculate work showing that specific activity, not overall activity level, drives afferent refinement
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claim_relations[4]0.85the tagger's words
claim_relationssupports → published rabies tracing of mature VIP interneurons showing no bias toward thalamic synapses
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claim_relations[5]1.0the tagger's words
concept_edgesNR2B —distinct-from→ NR2A
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differs in: THE AXIS IS WHICH SUBUNIT'S REMOVAL PRODUCES THE DEFECT. 'thalamocortical synapses use NMDA receptors (NMDARs) containing the NR2B subunit and ... Quotation withheld in Re+ interneurons.' Both subunits are present; only one is load-bearing for the morphology, and the contrast is a loss-of-function result rather than a difference in expression. · strength of the relation: 1
also in: NR2B · NR2A
concept_edges[2]1.0the tagger's words
concept_edgesEVIDENCE CORRECTED (RE-GROUNDED) · AMPAR —distinct-from→ NMDA
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EVIDENCE CORRECTED: RE-GROUNDED. The old span named only AMPARs. This sentence sets the two against each other in the paper's own construction - 'the contribution of NMDARs VERSUS AMPARs'. — strength of the relation: 0.95 · note: AMPAR signalling is present and explicitly insufficient, which is what makes the requirement receptor-specific rather than activity-general Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says interneurons failed to develop 'even in the presence of substantial signaling through AMPARs' when NMDARs were removed; distinct-from is implied, not stated.
also in: AMPAR · NMDA
concept_edges[3]1.0the tagger's words
concept_edgesEVIDENCE CORRECTED (RE-GROUNDED) · neurogliaform —distinct-from→ VIP
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EVIDENCE CORRECTED: RE-GROUNDED. The old span named only VIP. This sentence names both, says 'marked DIFFERENCES in the requirement for activity', and uses 'UNLIKE' between the two cell types. — strength of the relation: 1 · note: the built-in contrast: every manipulation impairing one leaves the other intact Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but this span says Re+ but not VIP+ interneurons were impaired; 'neurogliaform' is not named here, so distinct-from rests on the record's other span.
also in: neurogliaform · VIP
concept_edges[4]1.0the tagger's words
concept_edgesneurogliaform —distinct-from→ VIP
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differs in: THE AXIS IS WHETHER DEVELOPMENT REQUIRES ACTIVITY. 'We observed marked differences in the requirement for activity in VIP multipolar cells, which were apparently unaffected by attenuated levels of excitation, unlike Re+ neurogliaform cells, whose migration and morphological development were markedly impaired.' Two interneuron classes in the same manipulation, and only one needs the activity - so a study using either alone would conclude the opposite about interneuron development in general. · strength of the relation: 1 · note: RE-GROUNDS another row of this record: the old span named ONE endpoint.
also in: neurogliaform · VIP
concept_edges[5]1.0the tagger's words
concept_edgesAMPAR —distinct-from→ NMDA
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strength of the relation: 0.95 · note: RE-GROUNDS another row of this record: the old span named ONE endpoint.
also in: AMPAR · NMDA
concept_edges[6]1.0the tagger's words
content_tagsMann-Whitney U test
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content_tags.statistics[0]the tagger's words
content_tagst-test
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also in: t-test
content_tags.statistics[1]the tagger's words
content_tagsstandard error of the mean
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content_tags.statistics[2]the tagger's words
content_tagsp-value
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also in: p-value
content_tags.statistics[3]the tagger's words
content_tagsunpaired t-test on morphological measures
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content_tags.statistics[4]0.8the tagger's words
content_tagsproportion of presynaptic partners by source
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content_tags.statistics[5]1.0the tagger's words
content_tagsContrary to the classical view that layer IV is the main recipient of ascending sensory input, Reelin-expressing interneurons in layers I-III receive direct thalamic afferents during the first postnatal week.
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content_tags.findings[0]the tagger's words
content_tagsWhisker deprivation left cortical layering and interneuron migration intact but severely truncated the axons and dendrites of Reelin-expressing interneurons.
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content_tags.findings[1]the tagger's words
content_tagsThe results suggest thalamic activity is fundamental to the axo-dendritic development of Re+ interneurons.
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content_tags.findings[2]the tagger's words
content_tagsBlocking intracortical glutamate release, by contrast, left the morphological development of the same interneurons unaffected.
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content_tags.findings[3]the tagger's words
content_tagsLight-evoked NMDAR responses had a larger NR2B component with thalamic (VGlut2-ChR2) than with cortical (Emx1-ChR2) activation.
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content_tags.findings[4]the tagger's words
content_tagsThe maturation requirement is specific to NR2B: NR2A-null and AMPA-receptor-blocked interneurons developed normally.
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content_tags.findings[5]the tagger's words
content_tagsThe NMDA receptor requirement is confined to a narrow window between postnatal days 3 and 6.
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content_tags.findings[6]the tagger's words
content_tagsDeleting NR1 in these interneurons cut thalamic input from 60% to 16% and raised intracortical pyramidal input from 14% to 42%.
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content_tags.findings[7]the tagger's words
content_tagssuperficial Reelin interneurons receive direct thalamic input in the first postnatal week, contrary to the layer IV expectation
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content_tags.findings[8]1.0the tagger's words
content_tagseach interneuron received about 196 presynaptic partners, 56% of them thalamic
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content_tags.findings[9]1.0the tagger's words
content_tagsno appreciable input from dorsal raphe or nucleus basalis was found at this age
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content_tags.findings[10]1.0the tagger's words
content_tagsthe same tracing method did find nucleus basalis input to VIP and calretinin interneurons, so the absence is not a method artifact
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content_tags.findings[11]1.0the tagger's words
content_tagsremoving NMDA receptors cut thalamic input from 60% to 16% and raised intracortical from 14% to 42%
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content_tags.findings[12]1.0the tagger's words
content_tagsthe total number of presynaptic cells did not change
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content_tags.findings[13]1.0the tagger's words
content_tagsthe requirement falls between P3 and P6
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content_tags.findings[14]1.0the tagger's words
content_tagscortical layering and pyramidal cell distribution were normal despite the interneuron defects
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content_tags.findings[15]1.0the tagger's words
content_tagscells with rudimentary dendrites nonetheless received exuberant aberrant intracortical innervation
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content_tags.findings[16]1.0the tagger's words
content_tagsVAMP2
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also in: VAMP2
content_tags.definitions[0]the tagger's words
content_tagscritical period
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content_tags.definitions[2]1.0the tagger's words
content_tagschronic bilateral whisker plucking
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content_tags.variables[0]the tagger's words
content_tagsgenetic blockade
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content_tags.variables[1]the tagger's words
content_tagsthalamic afferent connectivity
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content_tags.variables[9]1.0the tagger's words
content_tagsintracortical pyramidal cell innervation
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content_tags.variables[10]1.0the tagger's words
content_tagsdendritic length
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content_tags.variables[11]the tagger's words
content_tagscomplexity of axonal arbors
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content_tags.variables[12]the tagger's words
content_tags196 ± 48 — mean number of presynaptic neurons traced to a single Reelin-expressing starter interneuron
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content_tags.quantities[0]the tagger's words
content_tags56 o 6% — share of traced presynaptic inputs originating in the VPM and POm thalamic nuclei (the ± sign is corrupted in the source text)
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content_tags.quantities[1]the tagger's words
content_tags30% ... 50% — share of all interneurons that are superficial Reelin- or VIP-expressing cells, in mouse versus human brain
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content_tags.quantities[2]the tagger's words
content_tags−83.89 ± 17.62 pA versus −3.60 ± 3.60 pA — mean intracortically evoked EPSC amplitude in control versus cortex-wide tetanus-toxin (Emx1-TeLC) mice, showing near-complete blockade
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content_tags.quantities[3]the tagger's words
content_tags190 ± 55 versus 150 ± 47; P = 0.646 — total presynaptic cells per starter cell in control versus NMDA-receptor-ablated interneurons, statistically indistinguishable
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content_tags.quantities[4]the tagger's words
content_tags60% ± 6 to 16% ± 2 — drop in the thalamic share of afferent connectivity after cell-autonomous NMDA receptor removal
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content_tags.quantities[5]the tagger's words
content_tags196 plus or minus 48 presynaptic neurons per interneuron, 56% thalamic, 14% local excitatory, 30% interneuron — the normal afferent composition
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content_tags.quantities[6]1.0the tagger's words
content_tagsthalamic 60% to 16%, intracortical 14% to 42%, interneuron 27% to 42% (n.s.) — the composition after NMDA receptor removal
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content_tags.quantities[7]1.0the tagger's words
content_tags190 versus 150 presynaptic cells, p = 0.646 — total input unchanged while composition flipped
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content_tags.quantities[8]1.0the tagger's words
content_tagsabout 10 ms EPSC latency — checked against prior studies using the same approach
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content_tags.quantities[9]1.0the tagger's words
content_tagsabout 30% of interneurons in mouse and 50% in human — the proportion of superficial interneurons across species
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content_tags.quantities[10]1.0the tagger's words

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