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A Distributed Network for Social Cognition Enriched for Oxytocin Receptors
Open accessAbstract
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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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.
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In the paper
“Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Abstract
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In the paper
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Abstract
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In the paper
“Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Abstract
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In the paper
“Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Abstract
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In the paper
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > OXTR-2, a novel and specific antibody to the mouse oxytocin receptor
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“the expression level was similar across the estrous cycle in virgin female auditory cortex or PVN ( p Ͼ 0.4 between estrous and proestrous, Student's unpaired two-tailed t test, n ϭ 3 animals in each state).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Oxytocin receptor expression in adult mouse brain
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“Positive labeling was detected in wild-type virgin female uterine tissue (Fig. 2D) and brain (Fig. 3).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > OXTR-2, a novel and specific antibody to the mouse oxytocin receptor
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“Our initial analysis indicated that all four antisera were positive.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > OXTR-2, a novel and specific antibody to the mouse oxytocin receptor
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In the paper
“Second, hippocampal CA2 in females had more OXTR-2ϩ cells than in other regions of the hippocampal formation (Fig. 4C, p Ͻ 0.01).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Oxytocin receptor expression in adult mouse brain
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“Finally, preadsorption of the OXTR-2 antibody with OXTR-2 pure peptide abolished the immunoreactivity observed with antibody alone in wild-type cortex (Fig. 2E).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > OXTR-2, a novel and specific antibody to the mouse oxytocin receptor
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- Probably not a substantial claim. 36
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“Oxytocin-receptor-expressing HEK cells were also immunostained with OXTR-2 and cells were colabeled for both OXTR-2 and Venus (Fig. 2C).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > OXTR-2, a novel and specific antibody to the mouse oxytocin receptor
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“No reactivity was observed in the preimmune bleeds, but higher levels of reactivity were observed with increasing amounts of OXTR-2 (Fig. 2A).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > OXTR-2, a novel and specific antibody to the mouse oxytocin receptor
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“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Subcellular localization of cortical oxytocin receptor expression
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“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 ).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Subcellular localization of cortical oxytocin receptor expression
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“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Development of cortical and thalamic oxytocin receptor expression
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“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
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“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
What the sources say
- Not checked yetcites Owen et al., 2013
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“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
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“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Marlin et al., 2015
- Not checked yetcites Owen et al., 2013
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“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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“Although IPSCs were reduced by oxytocin in auditory cortex and PVN when excitatory receptors were blocked, DNQX/APV prevented disinhibition in the piriform cortex.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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“Surprisingly, however, the predominant effect of oxytocin modulation is to reduce inhibitory transmission without directly affecting excitation.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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In the paper
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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“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)”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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- Also stated in: § Discussion · plain
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“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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In the paper
“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)”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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“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”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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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
“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)”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · 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
“Images from each brain area were collected and saved for manual counts by two independent blinded observers.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of OXTR-2ϩ cells.
plain- 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
“Experimenters were kept blind to the animal genotypes while capturing images and quantifying the frequency of immunolabeled profiles.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of oxytocinergic fiber densities.
plain- 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
“Quantification of OXTR-2ϩ cells in these animals was performed blind to estrous state.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of OXTR-2ϩ cells.
plainn = 6- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of oxytocinergic fiber densities.
What the sources say
- Not checked yetcites Peters et al., 1991
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. 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 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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Materials and Methods
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
“Recordings were excluded from analysis if R s or R i changed Ͼ30% compared with the baseline period.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of oxytocinergic fiber densities.
plain- Asserted: passes — The authors put it forward as true.
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- 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 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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of OXTR-2ϩ cells.
plain- 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
“qPCR assays were performed in triplicate per sample on 96-well plates.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of OXTR-2ϩ cells.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Synapses were categorized as symmetric and inhibitory if they lacked the thick PSDs (Peters et al., 1991).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of oxytocinergic fiber densities.
What the sources say
- Not checked yetcites Peters et al., 1991
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
“As a control, omission of primary antibody eliminated immunofluorescent labeling from that channel.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Materials and Methods
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.
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
“Wild-type and knockout animals were processed in parallel to ensure equalized labeling conditions.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of oxytocinergic fiber densities.
plain- 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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of oxytocinergic fiber densities.
plain- 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
“Controls lacking random hexamers, reverse transcriptase, or oxytocin receptor Taqman probe were run to verify the lack of contamination in the preparation.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of OXTR-2ϩ cells.
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
“EPSP slope is correlated with peak amplitude but less prone to contamination by polysynaptic activity (Staff and Spruston, 2003;Sweatt, 2009).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of oxytocinergic fiber densities.
What the sources say
- Not checked yetcites Staff and Spruston, 2003
- Not checked yetcites Sweatt, 2009
plaincorrelational- 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.
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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of OXTR-2ϩ cells.
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These 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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > OXTR-2, a novel and specific antibody to the mouse oxytocin receptor
boostedcorrelational- 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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Oxytocin receptor expression in adult mouse brain
hedgedconditional- 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
“Recordings were excluded from analysis if R s or R i changed Ͼ30% compared with the baseline period.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of oxytocinergic fiber densities.
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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Quantification of oxytocinergic fiber densities.
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.
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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.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Subcellular localization of cortical oxytocin receptor expression
What the sources say
- Not checked yetcites Marlin et al., 2015
- Not checked yetcites Owen et al., 2013
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.
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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
“Modulation and plasticity in these areas may be especially important for recognition of infant vocalizations, scents, and locations.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Oxytocin receptor expression in adult mouse brain
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.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Development of cortical and thalamic oxytocin receptor expression
What the sources say
- Not checked yetcites Owen et al., 2013
- Not checked yetcites Tyzio et al., 2006
- Not checked yetcites Tyzio et al., 2014
boosteddirect- 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
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Development of cortical and thalamic oxytocin receptor expression
What the sources say
- Not checked yetcites Dorrn et al., 2010
- Not checked yetcites Barkat et al., 2011
- Not checked yetcites Froemke and Jones, 2011
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that oxytocin receptors are poised at GABAergic synapses to control inhibitory transmission, perhaps by multiple presynaptic and postsynaptic mechanisms.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Subcellular localization of cortical oxytocin receptor expression
hedgedconditional- 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.
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
“suggesting that the mechanism of oxytocin modulation may be distinct in different brain areas, although the functional consequences may be similar.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
hedgedconditional- 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.
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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Development of cortical and thalamic oxytocin receptor expression
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that these effects are mediated directly by oxytocin receptor activation and not cross-reactivity of oxytocin peptide with other types of receptors.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
hedgeddirect- 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.
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
“During early postnatal development, when thalamic levels are high but layer 4 levels are low, oxytocin might independently modulate thalamic and intracortical circuits.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Development of cortical and thalamic oxytocin receptor expression
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.
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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Disinhibition can be effective for inducing long-term synaptic modifications in the auditory cortex (Froemke, 2015).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
What the sources say
- Not checked yetcites Froemke, 2015
plainconditional- 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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
boosteddirect- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data show conclusively that oxytocin disinhibits cortical neurons directly, boosting EPSP amplitude and converting subthreshold responses into suprathreshold spiking responses.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
boosteddirectSingle case- 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
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Nakajima et al., 2014
- Not checked yetcites Marlin et al., 2015
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.
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 leads to mechanisms of NMDA-receptor-dependent plasticity that consolidate these enhancements and enable them to persist in absence of further oxytocin action.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
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.
It may state two separate claims as one.
In the paper
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
What the sources say
- Not checked yetcites D'amour and Froemke, 2015
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Dorrn et al., 2010
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.
In the paper
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Gimpl and Fahrenholz, 2001 source
plainconditional- 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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Modulation of synaptic responses by oxytocin
hedgedconditional- 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
“Disinhibition seems to be a general mechanism for modulating cortical circuits (Kruglikov and Rudy, 2008;Froemke, 2015).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Kruglikov and Rudy, 2008
- Not checked yetcites Froemke, 2015
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.
In the paper
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Hitti and Siegelbaum, 2014
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Insel, 1990
- Not checked yetcites Jimenez et al., 2015
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. It may state two separate claims as one.
In the paper
“Moreover, oxytocin might directly stimulate hormone release from astrocytes (Parent et al., 2008).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Parent et al., 2008
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.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Kendrick et al., 1988
- Not checked yetcites Richard et al., 1991 source
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.
In the paper
“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).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
What the sources say
- Not checked yetcites Nakajima et al., 2014
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.
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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
hedgedconditional- Asserted: fails — The authors may not 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 authors may not put it forward as true. 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
“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.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
hedgedconditionaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Our study may have been underpowered to see more fine-grain differences in oxytocin receptors or oxytocinergic axon branches within individual circuits.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
hedged- 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
“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⍀).”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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.
- Also stated in: § Discussion · plain
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
“Oxytocin or gabazine enabled long-term plasticity of synaptic responses in vitro.”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
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.
It may state two separate claims as one.
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.”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, OXT from PVN increases the salience of mouse pup vocalizations, while a dam's experience with pups adjusts the balance of excitatory and inhibitory tuning in the auditory cortex (54,123,124).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [54]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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
The cited source says what the claim attributes to it.
In the citing paper
“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
In the citing paper
“The oxytocin receptor is expressed in several cortical areas, including A1, S1, mPFC, insular cortex, entorhinal cortex and piriform cortex (Knobloch et al., 2012; Mitre et al., 2016; Rogers-Carter et al., 2018; Sabihi et al., 2014).”
From Neuromodulation of maternal circuits by oxytocin (2019) · cites this paper as Mitre et al., 2016
In the citing paper
“optogenetic oxytocin release from axons can be induced at much lower stimulation frequency at increased duration of 5 Hz during 3 min in different brain structures ex vivo as A1, piriform cortex, and PVN itself, resulting in a decrease of inhibitory transmission and increased spiking output (Mitre et al., 2016).”
From Neuromodulation of maternal circuits by oxytocin (2019) · 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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Development of cortical and thalamic oxytocin receptor expression
“We found that this asymmetrical receptor expression was not present early in life, but emerged in the third postnatal week”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
“Lateralization was only apparent after the third postnatal week”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“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)”
§ Cellular/Molecular A Distributed Network for Social Cognition Enriched for Oxytocin Receptors > Discussion
Reported 145.5 · recomputed 141.666667
Citations
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
The oxytocin receptor system: structure, function, and regulation
Gimpl, G., & Fahrenholz, F. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.629 · Cited by 3,089
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Social effects of oxytocin in humans: context and person matter
Bartz, J. A., Zaki, J., Bolger, N., & Ochsner, K. N. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.05.002 · Cited by 1,581
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Mouse Estrous Cycle Identification Tool and Images
Byers, S. L., Wiles, M. V., Dunn, S. L., & Taft, R. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035538 · Cited by 1,220
The neurobiology of attachment
Insel, T. R., & Young, L. J. (2001) · Nature Reviews Neuroscience · doi:10.1038/35053579 · Cited by 1,173
Cited by
Sorted by citations
The oxytocin receptor: from intracellular signaling to behavior
Jurek, B., & Neumann, I. D. (2018) · Physiological Reviews · doi:10.1152/physrev.00031.2017 · Cited by 999
Oxytocin, Neural Plasticity, and Social Behavior
Froemke, R. C., & Young, L. J. (2021) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-102320-102847 · Cited by 480
“For example, oxytocin can shift auditory cortical frequency–tuning profiles for pure tones, similar to cholinergic modulation (Mitre et al. 2016).”
BackgroundMethodInfluentialSelf-citationHippocampal oxytocin receptors are necessary for discrimination of social stimuli
Raam, T., McAvoy, K. M., Besnard, A., Veenema, A. H., & Sahay, A. (2017) · Nature Communications · doi:10.1038/s41467-017-02173-0 · Cited by 292
Biased Oxytocinergic Modulation of Midbrain Dopamine Systems
Xiao, L., Priest, M. F., Nasenbeny, J., Lu, T., & Kozorovitskiy, Y. (2017) · Neuron · doi:10.1016/j.neuron.2017.06.003 · Cited by 292
Johnson, Z. V., & Young, L. J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.034 · Cited by 242
Metadata
- 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
- 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
- hybrid
- doi.org
- 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
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › 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.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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