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Cited by 305Neuroendocrine regulation and behaviorNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

A distributed network for social cognition enriched for oxytocin receptors

Open access
Mitre, Mariela, Marlin, Bianca J., Schiavo, Jennifer K., Morina, Egzona, Norden, Samantha E., Hackett, Troy A., Aoki, Chiye J., Chao, Moses V. +1 more·2016·The Journal of Neuroscience
DOI 10.1523/jneurosci.2409-15.2016PMC PMC4764667
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Abstract

Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent–infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition. SIGNIFICANCE STATEMENT Oxytocin is an important peptide hormone involved in maternal behavior and social cognition, but it has been unclear what elements of neural circuits express oxytocin receptors due to the paucity of suitable antibodies. Here, we developed new antibodies to the mouse oxytocin receptor. Oxytocin receptors were found in discrete brain regions and at cortical synapses for modulating excitatory-inhibitory balance and plasticity. These antibodies should be useful for future studies of oxytocin and social behavior.

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Written from the paper’s full text.

TL;DR

The paper reports a novel specific antibody (OXTR-2) against the mouse oxytocin receptor and maps receptor expression across the brain, identifying a female-enriched distributed network including piriform cortex, hippocampal CA2, and left auditory cortex. Functionally, oxytocin transiently reduced synaptic inhibition in several regions and enabled NMDA receptor-dependent long-term plasticity in auditory cortex.

Key findings

  • OXTR-2 was validated as specific: it detected a 43 kDa band in oxytocin-receptor-expressing HEK cells, labeled wild-type uterus and brain, and showed no labeling in oxytocin receptor knock-out tissue or after peptide preadsorption.
  • In adult mice, oxytocin receptors were widely expressed but enriched in specific regions: piriform cortex had more OXTR-2+ cells in females than males (p < 0.03); hippocampal CA2 had more OXTR-2+ cells than other hippocampal regions in females (p < 0.01); left auditory cortex had more OXTR-2+ cells than right auditory cortex in females (p < 0.002), with no lateralization in males (p > 0.9). Table 1 reported, for virgin females, left auditory cortex 26.5 ± 2.3% vs right 20.6 ± 3.0%, CA2 52.8 ± 5.9%, and piriform cortex 44.8 ± 7.5% vs males 10.5 ± 1.4%.
  • Electron microscopy showed OXTR-2 labeling at putative excitatory synapses (presynaptic: 6.3 ± 2.2% WT vs 1.4 ± 1.2% KO synapses, p < 10−4; postsynaptic spines: 22.0 ± 3.4% vs 3.7 ± 1.7%, p < 10−4), inhibitory synapses, axons, and glia, but not significantly in dendrites.
  • Oxytocin reduced evoked IPSCs in auditory cortex, piriform cortex, and PVN (e.g., auditory cortex 1 µM oxytocin decreased IPSCs to 80.7 ± 3.7% of baseline, n = 7, p < 0.003; piriform cortex 5 µM to 74.7 ± 4.5%, n = 6, p < 0.004; PVN 5 µM to 71.1 ± 5.3%, n = 5, p < 0.02), an effect blocked by the oxytocin receptor antagonist OTA. Oxytocin also enabled long-term potentiation and increased spike probability in auditory cortex, requiring NMDA receptors.

Methods

  • Custom polyclonal antibodies were generated against four mouse oxytocin receptor peptide sequences; OXTR-2 was affinity-purified and validated by dot blot, Western blot, immunohistochemistry in wild-type vs oxytocin receptor knock-out mice, and peptide preadsorption.
  • Receptor expression was quantified by confocal immunohistochemistry across 29 brain regions in experienced mothers, pup-naive adult virgin females, and adult males, with estrous state checked in some animals; additional methods included qPCR, RNAseq across postnatal ages, viral tracing of oxytocinergic axons, and electron microscopy in auditory cortex of 4 wild-type and 4 knock-out mice.
  • Synaptic function was tested with whole-cell recordings in acute slices from adult virgin female C57BL/6 or Oxt-IRES-Cre mice, using exogenous oxytocin, optogenetic release of endogenous oxytocin, and in vivo auditory cortex recordings with tone–oxytocin pairing.

Limitations

  • The paper states that receptor expression in some brain areas could be somewhat variable, that the study may have been underpowered to detect fine-grain differences in oxytocin receptors or oxytocinergic axon branches, and that animals were not behaviorally tested to control for paw preference or other functional lateralization.
  • The paper notes that topically applied oxytocin in vivo might diffuse to recorded cells 420–800 µm below the pial surface or act at more superficial synapses, and that mechanisms of oxytocin modulation may differ across regions (e.g., piriform cortex disinhibition was prevented by blocking excitation, unlike auditory cortex and PVN).
  • Evident from the text: the antibody is a custom polyclonal reagent validated in mouse, most functional experiments used virgin female mice and acute slices, and several proposed mechanisms (e.g., glial oxytocin receptor function, presynaptic vs postsynaptic actions) are hypotheses requiring further study.

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

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Crossref · 10.1523/jneurosci.2409-15.2016

Cites

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Claims the paper makes

0 of 51 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In the cerebral cortex, oxytocin receptors are mainly expressed at synapses, as well as on axons and glial processes.

    “Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes.”
    Quote in the paperNot a substantial claim
  • Findingown data

    A distributed network of female mouse brain regions for maternal behaviors is especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus.

    “We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus.”
    Quote in the paperSubstantial claim
  • Findingown data

    Oxytocin enables long-term synaptic plasticity in the auditory cortex.

    “Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex.”
    Quote in the paperSubstantial claim
  • Findingown data

    Oxytocin transiently reduces synaptic inhibition in multiple brain regions.

    “Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex.”
    Quote in the paperSubstantial claim
  • Findingown data

    No labeling was observed in oxytocin receptor knock-out mice anywhere in the brain or other tissues such as uterus, hypothalamic PVN, lateral septum, and neocortex.

    “In contrast, no labeling was observed in oxytocin receptor knock-out mice anywhere in the brain or other tissues such as uterus (Fig. 2D), hypothalamic PVN (Fig. 3A), lateral septum (Fig. 3B), and neocortex (Fig. 3C).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 36
  • May combine two claims. 45
  • The quote only partly states this claim. 2

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

    Findingown data

    Oxytocin-receptor-expressing HEK cells were immunostained with OXTR-2 and colabeled for both OXTR-2 and Venus.

    “Oxytocin-receptor-expressing HEK cells were also immunostained with OXTR-2 and cells were colabeled for both OXTR-2 and Venus (Fig. 2C).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    No reactivity was observed in the preimmune bleeds, but higher levels of reactivity were observed with increasing amounts of OXTR-2.

    “No reactivity was observed in the preimmune bleeds, but higher levels of reactivity were observed with increasing amounts of OXTR-2 (Fig. 2A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    OXTR-2 labeling was found at inhibitory synapses located both on dendritic shafts and perisomatically, as well as preterminal axon segments and glial cells.

    “OXTR-2 labeling was also found at inhibitory synapses located both on dendritic shafts and perisomatically (Fig. 6C,F, p Ͻ 0.01), as well as preterminal axon segments and glial cells (Fig. 6 D, E,G, p Ͻ 10 Ϫ4 for axonal labeling, p Ͻ 0.004 for glial labeling).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Oxytocin receptors were found at putative excitatory synapses, both at presynaptic terminals opposed to PSDs and also at PSDs themselves.

    “Oxytocin receptors were found at putative excitatory synapses, both at presynaptic terminals (Fig. 6 A, F, p Ͻ 10 Ϫ4 , Fisher's two-tailed exact test) opposed to PSDs and also at PSDs themselves (Fig. 6 B, D,F, p Ͻ 10 Ϫ4 ).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the auditory cortex, expression and mRNA levels were both low during the first postnatal week, but then increased abruptly at week two, decreasing thereafter to moderate levels in adults.

    “A different pattern was observed in the auditory cortex.Initially, expression and mRNA levels were both low during the first postnatal week, but then increased abruptly at week two, decreasing thereafter to moderate levels in adults (Fig. 7E, p Ͻ 10 Ϫ4 for OXTR-2 expression, p Ͻ 0.03 for mRNA).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Higher concentrations were required to reduce inhibition by a comparable degree in piriform cortex and PVN, with 5-10 M oxytocin reducing inhibition by a similar level in these two regions.

    “Higher concentrations were required to reduce inhibition by a comparable degree in piriform cortex (Fig. 9H ) and PVN (Fig. 9I ), with 5-10 M oxytocin reducing inhibition by a similar level in these two regions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Spontaneous rates of EPSCs and IPSCs were each increased in auditory cortex, piriform cortex, and PVN, with spontaneous inhibitory rates more than quadrupling in piriform cortex.

    “Strikingly, spontaneous rates of EPSCs and IPSCs were each increased in auditory cortex, piriform cortex, and PVN, with spontaneous inhibitory rates more than quadrupling in piriform cortex (Fig. 11 E, F ), similar to the effects of oxytocin receptor agonist application in hippocampal slices (Owen et al., 2013).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Owen et al., 2013

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    In a recording from virgin female left auditory cortex in vitro, oxytocin wash-in led to a gradual increase in EPSPs over 10-20 min, which persisted long after oxytocin washout, and the cell began firing action potentials.

    “Although excitation was initially unaffected, oxytocin wash-in (5 M) led to a gradual increase in EPSPs over 10 -20 min, which persisted long after oxytocin washout.In parallel, this cell began firing action potentials, eventually firing reliably on almost every trial.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Oxytocin receptors are widely expressed throughout the CNS and detectable in many brain areas.

    “Using a novel, specific antibody to the mouse oxytocin receptor OXTR-2, we found that oxytocin receptors were widely expressed throughout the CNS and detectable in many brain areas.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Oxytocin acts as a disinhibitory neuromodulator throughout the brain, rapidly decreasing evoked inhibitory events in the mouse piriform cortex and PVN, in the auditory cortex in vitro and in vivo, and in hippocampal neurons in vitro.

    “We and others have found that oxytocin acts as a disinhibitory neuromodulator throughout the brain, rapidly decreasing evoked inhibitory events in the mouse piriform cortex and PVN, in the auditory cortex in vitro and in vivo (Marlin et al., 2015), and in hippocampal neurons in vitro (Owen et al., 2013).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Marlin et al., 2015

      Not checked in the free run.

    • cites Owen et al., 2013

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    The reduction of inhibitory transmission by oxytocin was apparent after either pharmacological application of exogenous oxytocin or optogenetic release of endogenous oxytocin and was consistent across auditory cortex, piriform cortex, and PVN.

    “This was apparent after either pharmacological application of exogenous oxytocin or optogenetic release of endogenous oxytocin and was consistent across different brain areas: auditory cortex, piriform cortex, and PCtx).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Oxytocin receptors were located at excitatory and inhibitory synapses (both presynaptic and postsynaptic), along axons, and expressed by glial cells.

    “At the electron microscopic level, it appeared that oxytocin receptors were located at excitatory and inhibitory synapses (both presynaptic and postsynaptic), along axons, and expressed by glial cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    DNQX/APV prevented disinhibition in the piriform cortex but not in auditory cortex and PVN.

    “Although IPSCs were reduced by oxytocin in auditory cortex and PVN when excitatory receptors were blocked, DNQX/APV prevented disinhibition in the piriform cortex.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The predominant effect of oxytocin modulation is to reduce inhibitory transmission without directly affecting excitation.

    “Surprisingly, however, the predominant effect of oxytocin modulation is to reduce inhibitory transmission without directly affecting excitation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    OXTR-2 labeling is significantly higher in wild-type than knock-out animals in the cytoplasm of putative axon segments and glial cells, but not in dendrites.

    “Significant labeling was detected in the cytoplasm of putative axon segments (15.0 Ϯ 2.7% WT vs 3.0 Ϯ 1.3% KO, p Ͻ 10 Ϫ4 ) and glial cells (12.4 Ϯ 2.5% WT vs 7.7 Ϯ 1.9% KO, p Ͻ 0.004), but not dendrites (2.5 Ϯ 1.3% WT vs 1.5 Ϯ 1.0% KO, p Ͼ 0.1).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Exogenous oxytocin (1 μM) reduces IPSC amplitude in layer 5 pyramidal neurons of mouse auditory cortex in vitro.

    “Oxytocin (1 m) washed into the bath decreased IPSC amplitude (baseline: 262.7 Ϯ 5.1 pA, 3-6 min after start of wash-in: 209.9 Ϯ 7.8 pA, reduced to 79.9% of baseline).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Oxytocin reduces IPSCs in auditory cortex and PVN but not piriform cortex in the presence of DNQX/APV.

    “Oxytocin reduced IPSCs in DNQX/APV (25 and 50 M) in auditory cortex and PVN but not piriform cortex (auditory cortex 1 M oxytocin, decrease to 73.1 Ϯ 5.3% of baseline, n ϭ 8, p Ͻ 0.002; piriform cortex 5 M oxytocin, 94.2 Ϯ 2.8% of baseline, n ϭ 5, p Ͼ 0.1; PVN 5 M oxytocin, decrease to 86.9 Ϯ 2.2% of baseline, n ϭ 5, p Ͻ 0.005).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Oxytocin increases EPSP slope and spiking probability in layer 5 pyramidal neurons of mouse auditory cortex in vitro.

    “Oxytocin (OT, 5 m, red bar) washed into the bath gradually increased EPSP slope (baseline: 6.9 Ϯ 0.1 mV/msec, 10 -20 min after start of wash-in: 8.3 Ϯ 0.1 mV/msec, increased to 120.6% of baseline) and spiking probability (upper raster plot, baseline: 4.0% of trials, 10 -20 min after wash-in: 96.3% of trials; cell was depolarized by 19 mV).”
    • Also stated in: § Discussion · plain
      “Mean change in EPSP slope after oxytocin wash-in (5 M, mean increase to 117.7 Ϯ 7.2% of baseline, n ϭ 10, p Ͻ 0.04; Student's paired two-tailed t test)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Gabazine increases EPSP slope and spiking probability in auditory cortex in vitro.

    “Gabazine (0.1 m, black bar) washed into the bath gradually increased EPSP slope (baseline: 4.8 Ϯ 0.1 mV/msec, 10 -20 min after start of wash-in: 6.8 Ϯ 0.1 mV/msec, increased to 145.5% of baseline) and spiking probability (upper raster plot, baseline: 6.3% of trials, 10 -20 min after wash-in: 100.0% of trials; cell was depolarized by 12 mV).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Oxytocin does not enhance EPSP slope or spiking probability in auditory cortex in the presence of APV.

    “Oxytocin wash-in (5 m oxytocin, red bar) in the presence of APV (50 m APV, black bar) did not enhance EPSP slope (baseline: 6.6 Ϯ 0.1 mV/msec, 10 -20 min after wash-in: 5.5 Ϯ 0.1 mV/msec, decreased to 83.1% of baseline) or spiking probability (upper raster plot, baseline: 20.8% of trials, 10 -20 min after wash-in: 10.0% of trials; cell was depolarized by 12 mV).”
    • Also stated in: § Discussion · plain
      “oxytocin in APV (5 M oxytocin, 50 M APV, 97.2 Ϯ 10.2% of baseline, n ϭ 6, p Ͼ 0.7)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Oxytocin increases spontaneous EPSC and IPSC frequency in auditory cortex, piriform cortex, and PVN.

    “Oxytocin increased spontaneous event frequency (auditory cortex 1 M oxytocin, spontaneous EPSC frequency increased to 133.1 Ϯ 10.3% of baseline, p Ͻ 0.04; auditory cortex spontaneous IPSC frequency increased to 169.5 Ϯ 17.6% of baseline, p Ͻ 0.03; piriform cortex 5 M oxytocin, spontaneous EPSC frequency increased to 151.3 Ϯ 19.1% of baseline, p Ͻ 0.05; piriform cortex spontaneous IPSC frequency”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Optogenetic release of oxytocin increases EPSP slope and spiking probability in auditory cortex in vitro.

    “Optogenetic release of oxytocin (Opto, blue bar) increased EPSP slope (baseline: 2.5 Ϯ 0.1 mV/msec, 10 -20 min after start of optogenetic stimulation: 3.5 Ϯ 0.05 mV/msec, increased to 141.6% of baseline) and spiking probability (upper raster plot, baseline: 18.2% of trials, 10 -20 min after start of optogenetic stimulation: 48.7% of trials; cell was depolarized by 19 mV).”
    • Also stated in: § Discussion · plain
      “optogenetic release of oxytocin (mean increase to 119.3 Ϯ 5.4% of baseline, n ϭ 5, p Ͻ 0.03)”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Manual counts of immunoreactive cells were performed by two independent blinded observers.

    “Images from each brain area were collected and saved for manual counts by two independent blinded observers.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Experimenters were kept blind to animal genotypes while capturing images and quantifying the frequency of immunolabeled profiles.

    “Experimenters were kept blind to the animal genotypes while capturing images and quantifying the frequency of immunolabeled profiles.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Quantification of OXTR-2+ cells in estrous-staged animals was performed blind to estrous state.

    “Quantification of OXTR-2ϩ cells in these animals was performed blind to estrous state.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Asymmetric synapses are excitatory and are identified by thick postsynaptic densities.

    “Asymmetric synapses were identified by thick postsynaptic densities (PSDs) on a portion of membrane adjacent to a vesicle-filled axon terminal and were presumably excitatory.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Peters et al., 1991

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Brains of wild-type and knock-out animals were processed together to minimize confounding factors, and parallel sections from knock-out animals served as controls.

    “The brains of wild-type and knock-out animals were processed together to minimize any confounding factors and parallel sections from knock-out animals served as controls.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Recordings were excluded from analysis if series resistance or input resistance changed >30% compared with baseline.

    “Recordings were excluded from analysis if R s or R i changed Ͼ30% compared with the baseline period.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The distribution and number of immunoreactive cells in each section were determined by taking images of wild-type and knock-out sections under the same laser power output, pinhole aperture, and gain.

    “The distribution and number of immunoreactive cells in each section were determined by taking images of wild-type and knock-out sections under the same laser power output, pinhole aperture, and gain.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    qPCR assays were performed in triplicate per sample.

    “qPCR assays were performed in triplicate per sample on 96-well plates.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Synapses lacking thick postsynaptic densities are categorized as symmetric and inhibitory.

    “Synapses were categorized as symmetric and inhibitory if they lacked the thick PSDs (Peters et al., 1991).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Peters et al., 1991

      Not checked in the free run.

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

    Study design and conductown data

    Omission of primary antibody eliminated immunofluorescent labeling from that channel.

    “As a control, omission of primary antibody eliminated immunofluorescent labeling from that channel.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Wild-type and oxytocin receptor knock-out animals were processed in parallel to ensure equalized labeling conditions.

    “Wild-type and knockout animals were processed in parallel to ensure equalized labeling conditions.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Micrographs were captured randomly, except for the constraint of imaging as close as possible to the EPON-tissue interface, regardless of whether an immunolabeled profile was present in the field.

    “This procedure ensured that micrographs were captured randomly, except for the constraint of imaging as close as possible to the EPON-tissue interface, regardless of whether an immunolabeled profile was present in the field.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    qPCR controls lacking random hexamers, reverse transcriptase, or oxytocin receptor Taqman probe verified lack of contamination in the preparation.

    “Controls lacking random hexamers, reverse transcriptase, or oxytocin receptor Taqman probe were run to verify the lack of contamination in the preparation.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    EPSP slope is correlated with peak amplitude but less prone to contamination by polysynaptic activity.

    “EPSP slope is correlated with peak amplitude but less prone to contamination by polysynaptic activity (Staff and Spruston, 2003;Sweatt, 2009).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Staff and Spruston, 2003

      Not checked in the free run.

    • cites Sweatt, 2009

      Not checked in the free run.

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

    Study design and conductown data

    Oxytocin receptor mRNA levels of left and right auditory cortex were compared by Student's paired two-tailed t test because the data passed Kolmogorov-Smirnov normality tests.

    “Oxytocin receptor mRNA levels of left and right auditory cortex were compared by Student's paired two-tailed t test because the data passed Kolmogorov-Smirnov normality tests.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The OXTR-2 antibody is highly specific for the mouse oxytocin receptor and binds to the target epitope sequence on the oxytocin receptor.

    “These experiments demonstrate that the OXTR-2 antibody is highly specific for the mouse oxytocin receptor and that the antibody binds to the target epitope sequence on the oxytocin receptor.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Although oxytocin may act throughout the brain, there are specific areas related to maternal behaviors that may be especially sensitive to oxytocinergic modulation in female mice beyond the hypothalamus: hippocampal CA2, piriform cortex, and left auditory cortex.

    “These findings indicate that, although oxytocin may act throughout the brain, there are specific areas related to ma-ternal behaviors that may be especially sensitive to oxytocinergic modulation in female mice beyond the hypothalamus: hippocampal CA2, piriform cortex, and left auditory cortex.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Recordings were excluded from analysis if series resistance (Rs) or input resistance (Ri) changed more than 30% compared with the baseline period.

    “Recordings were excluded from analysis if R s or R i changed Ͼ30% compared with the baseline period.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    To ensure recordings or implants were targeted to A1, multiunit activity was recorded and A1 was mapped with pure tones.

    “To ensure recordings or implants were targeted to A1, we first recorded multiunit activity with tungsten electrodes.A1 was mapped with pure tones (60 dB SPL, 2-79 kHz at 0.2-1 octave steps, 50 ms duration, 1-3 ms cosine on/off ramps) delivered in a pseudorandom sequence at 0.5-1 Hz.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Oxytocin modulates GABAergic transmission in neocortical and hippocampal circuits.

    “Inhibitory synapse expression is interesting given recent studies by us (Marlin et al., 2015) and others (Owen et al., 2013) showing that oxytocin modulates GABAergic transmission in neocortical and hippocampal circuits.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Marlin et al., 2015

      Not checked in the free run.

    • cites Owen et al., 2013

      Not checked in the free run.

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

    Interpretationreasoning

    Modulation and plasticity in these areas may be especially important for recognition of infant vocalizations, scents, and locations.

    “Modulation and plasticity in these areas may be especially important for recognition of infant vocalizations, scents, and locations.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Oxytocin can reduce the efficacy of GABAergic transmission as either an inhibitory or excitatory neurotransmitter.

    “An interesting set of studies has recently examined oxytocin modulation in the perinatal and postnatal rodent hippocampus, demonstrating that oxytocin can reduce the efficacy of GABAer- gic transmission as either an inhibitory (Owen et al., 2013) or excitatory (Tyzio et al., 2006;Tyzio et al., 2014) neurotransmitter.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Owen et al., 2013

      Not checked in the free run.

    • cites Tyzio et al., 2006

      Not checked in the free run.

    • cites Tyzio et al., 2014

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

    Premisecitation

    The second and third weeks are important stages for auditory cortical development, with hearing onset in rodents beginning around P10, the critical period for tonotopic map organization occurring over the next few days, and the development of excitatory-inhibitory balance progressing into the end of the third postnatal week.

    “The second and third weeks are important stages for auditory cortical development, with hearing onset in rodents beginning around P10, the critical period for tonotopic map organization occurring over the next few days, and the development of excitatory-inhibitory balance progressing into the end of the third postnatal week (Dorrn et al., 2010;Barkat et al., 2011;Froemke and Jones, 2011).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Dorrn et al., 2010

      Not checked in the free run.

    • cites Barkat et al., 2011

      Not checked in the free run.

    • cites Froemke and Jones, 2011

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Oxytocin receptors are poised at GABAergic synapses to control inhibitory transmission, perhaps by multiple presynaptic and postsynaptic mechanisms.

    “These data suggest that oxytocin receptors are poised at GABAergic synapses to control inhibitory transmission, perhaps by multiple presynaptic and postsynaptic mechanisms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The mechanism of oxytocin modulation may be distinct in different brain areas, although the functional consequences may be similar.

    “suggesting that the mechanism of oxytocin modulation may be distinct in different brain areas, although the functional consequences may be similar.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    Thereafter, the oxytocin-receptor-expressing cells might mature along a layer-specific program, first in the superficial layers and then in deep layers, before expression occurs or cells mature within layer 4.

    “Thereafter, the oxytocin-receptor-expressing cells might mature along a layer-specific program, first in the superficial layers and then in deep layers, before expression occurs or cells mature within layer 4.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    These effects are mediated directly by oxytocin receptor activation and not cross-reactivity of oxytocin peptide with other types of receptors.

    “indicating that these effects are mediated directly by oxytocin receptor activation and not cross-reactivity of oxytocin peptide with other types of receptors.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    During early postnatal development, when thalamic levels are high but layer 4 levels are low, oxytocin might independently modulate thalamic and intracortical circuits.

    “During early postnatal development, when thalamic levels are high but layer 4 levels are low, oxytocin might independently modulate thalamic and intracortical circuits.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    In piriform cortex, excitatory cells and synapses onto inhibitory cells might be affected by oxytocin, increasing inhibitory tone and hyperpolarization to reduce excitatory drive onto inhibitory cells.

    “However, in piriform cortex, excitatory cells and synapses onto inhibitory cells might be affected by oxytocin, increasing inhibitory tone and hyperpolarization to reduce excitatory drive onto inhibitory cells.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Disinhibition can be effective for inducing long-term synaptic modifications in the auditory cortex.

    “Disinhibition can be effective for inducing long-term synaptic modifications in the auditory cortex (Froemke, 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Froemke, 2015

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The long-term changes produced by a brief period of oxytocin wash-in required NMDA receptors, strongly suggesting that this enhancement of EPSP strength is a canonical form of LTP.

    “Therefore, the long-term changes produced by a brief period of oxytocin wash-in required NMDA receptors, strongly suggesting that this enhancement of EPSP strength is a canonical form of LTP.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Oxytocin disinhibits cortical neurons directly, boosting EPSP amplitude and converting subthreshold responses into suprathreshold spiking responses.

    “These data show conclusively that oxytocin disinhibits cortical neurons directly, boosting EPSP amplitude and converting subthreshold responses into suprathreshold spiking responses.”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    Receptor lateralization might be part of a maturational program for specific types of cortical interneurons, including a subset of parvalbumin-positive and somatostatin-positive inhibitory cells that predominantly express oxytocin receptors.

    “It is possible that receptor lateralization might be part of a maturational program for specific types of cortical interneurons, including a subset of parvalbumin-positive and somatostatinpositive inhibitory cells that predominantly express oxytocin receptors (Nakajima et al., 2014;Marlin et al., 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Nakajima et al., 2014

      Not checked in the free run.

    • cites Marlin et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    This leads to mechanisms of NMDA-receptor-dependent plasticity that consolidate these enhancements and enable them to persist in absence of further oxytocin action.

    “This leads to mechanisms of NMDA-receptor-dependent plasticity that consolidate these enhancements and enable them to persist in absence of further oxytocin action.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    A consequence of the disinhibitory action of oxytocin modulation is to enable LTP induction, likely by increasing synaptic strength from a subthreshold to a suprathreshold level and consequently inducing excitatory STDP.

    “These data support the hypothesis that a consequence of the disinhibitory action of oxytocin modulation is to enable LTP induction, likely by increasing synaptic strength from a subthreshold to a suprathreshold level and consequently inducing excitatory STDP (D'amour and Froemke, 2015).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites D'amour and Froemke, 2015

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Inhibitory responses begin to mature during the third postnatal week in the rodent auditory cortex.

    “Lateralization was only apparent after the third postnatal week, which is particularly significant given that inhibitory responses begin to mature during this period in the rodent auditory cortex (Dorrn et al., 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Dorrn et al., 2010

      Not checked in the free run.

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

    Premisecitation

    The oxytocin receptor is under tremendous control by various regulatory elements that provide potential for asymmetric expression.

    “The potential mechanisms for this surprising lateralization of both protein and transcript levels is unclear, but the oxytocin receptor is under tremendous control by various regulatory elements that provide potential for asymmetric expression (Gimpl and Fahrenholz, 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gimpl and Fahrenholz, 2001 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Oxytocin might transiently increase the salience of incoming sensory input, enabling cortical circuits (and other oxytocin-sensitive brain regions) to form new memories of important social experiences.

    “In this way, oxytocin might transiently increase the salience of incoming sensory input, enabling cortical circuits (and other oxytocin-sensitive brain regions) to form new memories of important social experiences.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Disinhibition seems to be a general mechanism for modulating cortical circuits.

    “Disinhibition seems to be a general mechanism for modulating cortical circuits (Kruglikov and Rudy, 2008;Froemke, 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Kruglikov and Rudy, 2008

      Not checked in the free run.

    • cites Froemke, 2015

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The CA2 region of the hippocampus conveys signals to promote social interaction and memory.

    “The abundance of oxytocin receptor expression in CA2 is particularly significant given the finding that this region of the hippocampus conveys signals to promote social interaction and memory (Hitti and Siegelbaum, 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Hitti and Siegelbaum, 2014

      Not checked in the free run.

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

    Interpretationreasoning

    The lack of estrous regulation may be a consequence of the rapid estrous cycling in mice and is comparable to findings examining radiolabeled oxytocin receptors in maternal rats and rabbits.

    “This may be a consequence of the rapid estrous cycling in mice and is comparable to findings examining radiolabeled oxytocin receptors in maternal rats (Insel, 1990) and rabbits (Jimenez et al., 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Insel, 1990

      Not checked in the free run.

    • cites Jimenez et al., 2015

      Not checked in the free run.

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

    Premisecitation

    Oxytocin might directly stimulate hormone release from astrocytes.

    “Moreover, oxytocin might directly stimulate hormone release from astrocytes (Parent et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Parent et al., 2008

      Not checked in the free run.

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

    Interpretationcitation

    Optogenetic stimulation of oxytocinergic fibers may lead to corelease of other neurotransmitters or neuromodulators that regulate inhibition, such as glutamate.

    “It is also possible that optogenetic stimulation of oxytocinergic fibers leads to corelease of other neurotransmitters or neuromodulators that regulate inhibition, such as glutamate (Kendrick et al., 1988;Richard et al., 1991).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Kendrick et al., 1988

      Not checked in the free run.

    • cites Richard et al., 1991 source

      Not checked in the free run.

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

    Premisecitation

    Somatostatin-positive inhibitory cells in mouse frontal cortex express oxytocin receptors.

    “This is similar to a recent study in transgenic mice in which somatostatin-positive inhibitory cells in mouse frontal cortex were found to express oxytocin receptors (Nakajima et al., 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nakajima et al., 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    In the auditory cortex and PVN, oxytocin receptors on presynaptic inhibitory terminals might directly decrease GABA release, whereas in the piriform cortex, oxytocin receptor activation might hyperpolarize excitatory cells, preventing them from driving inhibitory cells.

    “In the auditory cortex and PVN, we hypothesize that oxytocin receptors on presynaptic inhibitory terminals might directly decrease GABA release, whereas in the piriform cortex, oxytocin receptor activation might hyperpolarize excitatory cells, preventing them from driving inhibitory cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Although inhibitory events were consistently reduced in auditory cortex, piriform cortex, and PVN, there may be important distinctions in the mechanisms and details of oxytocinergic modulation in different circuits.

    “Although inhibitory events were consistently reduced in each of the three brain regions examined here (auditory cortex, piriform cortex, and PVN), there may be important distinctions in the mechanisms and details of oxytocinergic modulation in different circuits.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Our study may have been underpowered to see more fine-grain differences in oxytocin receptors or oxytocinergic axon branches within individual circuits.

    “Our study may have been underpowered to see more fine-grain differences in oxytocin receptors or oxytocinergic axon branches within individual circuits.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    In the recorded neurons, input resistance (R_i) and series resistance (R_s) remained stable during oxytocin wash-in.

    “R i and R s for this experiment, which each changed Ͻ10% from baseline during wash-in.”
    • Also stated in: § Discussion · plain
      “R i changed Ͻ5% and R s changed ϳ20% from baseline during wash-in.”
    • Also stated in: § Discussion · plain
      “R i of this neuron was stable (mean R i before wash-in: 165.5 M⍀, mean R i 10 -20 min after wash-in: 166.8 M⍀).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Oxytocin or gabazine enables long-term plasticity of synaptic responses in vitro.

    “Oxytocin or gabazine enabled long-term plasticity of synaptic responses in vitro.”
    Quote in the paperSubstantial claim
71 of 71

  • The paper relies on this without support.

    The oxytocin receptor knock-out mice used as controls lack oxytocin receptor protein.

    “tissues from the oxytocin-receptor knock-out uterus and brain, were used as controls in each Western blot analysis.”
    “oxytocin receptor knock-out brain sections”

  • The paper relies on this without support.

    The distribution of oxytocin receptors in the mouse brain determines which components of neural circuits are directly sensitive to oxytocin modulation and thus form an important network for control of social behavior.

    “The distribution of oxytocin receptors in the mouse brain determines which components of neural circuits are directly sensitive to oxytocin modulation and thus form an important network for control of social behavior.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Pairing oxytocin with synaptic stimulation persistently increases EPSCs and spiking.

    “Pairing oxytocin with synaptic stimulation persistently increases EPSCs and spiking”

    From Oxytocin, Neural Plasticity, and Social Behavior (2021) · cites this paper as Mitre et al. 2016

    In “Modulation of synaptic responses by oxytocin” (page unavailable), the paper reports that repetitive stimulation with oxytocin produced persistent EPSP potentiation and increased spiking. The Discussion (page unavailable) explicitly says that potentiation of EPSCs was not observed. The claim is therefore supported for spiking, but substitutes EPSCs for the reported EPSPs. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Oxytocin can shift auditory cortical frequency-tuning profiles for pure tones, similar to cholinergic modulation.

    “For example, oxytocin can shift auditory cortical frequency–tuning profiles for pure tones, similar to cholinergic modulation (Mitre et al. 2016).”

    From Oxytocin, Neural Plasticity, and Social Behavior (2021) · cites this paper as Mitre et al. 2016

    The ‘Modulation of synaptic responses by oxytocin’ section reports lasting changes in auditory-cortical frequency tuning after pure tones were paired with oxytocin; Figure 13 shows increased responses at the paired frequency. Our copy does not establish the claimed similarity to cholinergic modulation. Page numbers were not available in the indexed passages. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Oxytocinergic axons are found throughout the brain, including in the thalamus, cortex, amygdala, striatum, and hippocampus.

    “revealed oxytocinergic axons throughout the brain, including in the thalamus, cortex, amygdala, striatum, and hippocampus”

    From Oxytocin, Neural Plasticity, and Social Behavior (2021) · cites this paper as Mitre et al. 2016

    The ‘Oxytocinergic axonal projections’ section reports oxytocinergic fibers in several cortical areas and YFP-labeled axons in the hippocampus; the Discussion also describes oxytocin-releasing axons in many diverse regions. Our copy does not establish the claimed axonal presence specifically in the thalamus, amygdala, or striatum. Its passages naming those areas concern oxytocin receptors, not oxytocinergic axons (page numbers unavailable). (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Cortical oxytocin receptors are found primarily on parvalbumin-positive or somatostatin-positive inhibitory interneurons, including at inhibitory synaptic terminals.

    “Cortical oxytocin receptors are found primarily on parvalbumin-positive or somatostatin-positive inhibitory interneurons”

    From Oxytocin, Neural Plasticity, and Social Behavior (2021) · cites this paper as Mitre et al. 2016

  • Only a fraction of neurons seem to express oxytocin receptors.

    “only a fraction of neurons seem to express oxytocin receptors”

    From Oxytocin, Neural Plasticity, and Social Behavior (2021) · cites this paper as Mitre et al. 2016

Self-check

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

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting timing of auditory-cortex receptor lateralization

    Minor

    The results say lateralization emerged during the third postnatal week, whereas the discussion says it was apparent only after that week.

  • Gabazine-associated EPSP increase does not match the reported slopes

    Minor

    The reported EPSP slopes give 6.8 ÷ 4.8 × 100 = 141.7% of baseline, not 145.5%. Even allowing for rounding of both slopes to one decimal place cannot produce 145.5%.

    Reported 145.5 · recomputed 141.666667

2 of 2

Cites

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Authors
Mitre, M., Marlin, B. J., Schiavo, J. K., Morina, E., Norden, S. E., Hackett, T. A., Aoki, C. J., Chao, M. V., & Froemke, R. C.
Affiliations
  • New York University (US)
  • Vanderbilt University (US)
  • NYU Langone Health (US)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2016-02-24
Volume
36
Issue
8
Pages
2517-2535
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.2409-15.2016
PMC
PMC4764667
OpenAlex
W2278486104
Semantic Scholar
c126acf168845fd8cf6d327647b26e130894ac18
Cited by
305
References
71
Citations by year
2026: 23 · 2025: 19 · 2024: 31 · 2023: 24 · 2022: 44 · 2021: 39 · 2020: 45 · 2019: 12 · 2018: 31 · 2017: 28 · 2016: 8
FWCI
41.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • McKnight Foundation
  • Vanderbilt University
  • National Institutes of Health (HD015052, NS-21072, EY13079)
  • Vanderbilt Kennedy Center, Vanderbilt University Medical Center
  • National Institute of Mental Health (R21MH105846, T32MH019524)
  • National Eye Institute (EY 13079, P30EY013079)
  • National Institute on Deafness and Other Communication Disorders (DC012527, K99DC009635, R01DC009836, DC009635, R00DC009635, K18DC012527, R01DC015388, DC009836, R01DC012557)
  • National Institute of Neurological Disorders and Stroke (R01NS021072, NS-21072, R56NS021072, T32NS086750)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD015052, P30-HD015052-33, U54HD083211)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
oxytocin receptor, oxytocin, maternal behavior, social cognition, piriform cortex, auditory cortex, hippocampal CA2, synaptic inhibition, excitation-inhibition balance, synaptic plasticity, glial processes, antibody development, parent-infant bonding
MeSH terms
Amino Acid Sequence, Animals, Auditory Cortex, Cognition, Female, Humans, Male, Mice, Inbred C57BL, Molecular Sequence Data, Nerve Net, Social Behavior, Receptors, Oxytocin, Mice, Knockout, Mice, HEK293 Cells

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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.

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