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Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance
Open accessPublished version of a preprint
Abstract
Significance: The neuropeptide oxytocin is an important regulator of social behavior and is widely considered to reduce anxiety-related behaviors. However, growing evidence suggests that sometimes oxytocin increases anxiety. How can the same molecule have such different effects on behavior? Here we provide evidence that oxytocin produced outside of the hypothalamus is necessary and sufficient for stress-induced social anxiety behaviors. This suggests that the diverse effects of oxytocin on anxiety-related behaviors are mediated by circuit-specific oxytocin action.
Overview
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Written from the paper’s full text.
TL;DR
In female California mice, oxytocin synthesis in medioventral bed nucleus of the stria terminalis (BNSTmv) is necessary for social defeat–induced reductions in social approach and increases in social vigilance. BNSTmv oxytocin neurons project to anteromedial BNST (BNSTam), where oxytocin infusion is sufficient to induce social avoidance and vigilance in stress-naïve males and females.
Key findings
- BNSTmv antisense morpholino reduced oxytocin-immunoreactive cells compared with missense controls (F1,28=5.4, p=0.02) and prevented stress-induced reductions in social approach (stress×treatment F1,31=5.7, p=0.02) and increases in social vigilance (stress×treatment F1,31=6.2, p=0.02) in female California mice.
- Male California mice tested 10 min after a third social defeat episode showed reduced social approach (t14=2.46, p=0.02, d=1.23) and increased social vigilance (t14=2.36, p=0.03, d=1.18) versus naïve males.
- Viral tracing showed BNSTmv oxytocin neurons project to BNSTam and anterior/lateral hypothalamus; on average 63% of oxytocin-immunoreactive cells expressed Venus, and all Venus-positive cells coexpressed oxytocin.
- Oxytocin infusion into BNSTam in stress-naïve mice reduced social approach and increased social vigilance; in females, 1.0 ng reduced approach (p<0.001, d=4.8) and increased vigilance (p<0.001, d=2.3), and in males, 1.0 ng reduced approach (p=0.00, d=1.93) and increased vigilance (p<0.001, d=1.27). In C57BL/6 mice, vicarious defeat increased vigilance in females (p<0.0001, d=1.9) and BNST oxytocin cell number (t14=2.721, p=0.01, d=1.4), but not PVN oxytocin cells.
Methods
- California mice underwent social defeat or control handling; one week later, females received BNSTmv antisense or missense morpholino injections, followed by social interaction testing. Male California mice were tested 10 min after a third defeat episode.
- C57BL/6 mice underwent vicarious social defeat or control handling and social interaction testing; BNST and PVN oxytocin cells were assessed immunohistochemically.
- Circuit mapping used AAV-OTpr-Venus tracing from BNSTmv; qPCR and fluorescent in situ hybridization assessed Oxtr/Gad1/vGlut2 in BNSTam; site-specific oxytocin infusions into BNSTam were tested in stress-naïve females and males. Analyses used 2-way ANOVAs, t-tests, planned comparisons, and Cohen’s d.
Limitations
- Stated: the authors do not know whether BNST oxytocin neurons synapse within target regions, and non-synaptic/periaxonal or en passant release is possible; a role of PVN oxytocin is not excluded; future single-cell analysis is needed to understand how Oxtr activation in BNSTam modulates behavior.
- Evident: oxytocin synthesis knockdown in BNSTmv was tested only in female California mice, while males received acute defeat testing and BNSTam oxytocin infusion but not antisense knockdown.
- Evident: the study does not directly measure oxytocin release in BNSTam during stress or social interaction.
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Claims the paper makes
56 Own result · 20 Not checked yet · 17 Own interpretation · 4 Own method
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
“Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Abstract
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In the paper
“Oxytocin knock-down prevented stress-induced increases in social vigilance and decreases in social approach.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Abstract
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In the paper
“First, we used real-time PCR to assess whether there were basal or stress-induced sex differences in Oxtr expression within the BNSTam and there were no differences (fig., 3I).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The effect of social defeat on social approach, measured by time spent in the interaction zone, was dependent on antisense treatment (F 1,31 =5.7, p=0.02, fig.1E).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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In the paper
“There were no effects of BNST antisense infusions on PVN oxytocin cells (supplementary fig.1F), indicating oxytocin knockdown in the BNST was site-specific.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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In the paper
“Planned comparisons revealed that compared to missense, antisense reduced oxytocin immunoreactive cells in stressed (p=0.03,d=1), but not in control females.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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In the paper
“We also observed fibers in hypothalamic areas including anterior fig.3F) and lateral (Fig. 3G) hypothalamus.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When Venus expression was exclusively limited to BNSTmv neurons, we found that in both males and females BNSTmv oxytocin neurons sent fibers to more anterior areas of the BNST including dorsal (fig.3D) and ventral (fig.3E) subregions of the BNSTam.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“An alternate schedule of multiple injections of a lower dose of morpholino antisense also reduced oxytocin cell number in the BNSTmv (stress missense vs. stress antisense p=0.01, d=1.16, supplementary fig.1H,1I).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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In the paper
“Immunohistochemical analyses of oxytocin cells in females showed that the distribution of oxytocin positive cells within the BNST was limited to ventral BNST near bregma 0.02 (fig.2C), similar to California mice (Steinman et al., 2016) and rats (DiBenedictis et al., 2017).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
What the sources say
- Not checked yetcites Steinman et al., 2016
- Not checked yetcites DiBenedictis et al., 2017
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In the paper
“Overall, antisense reduced the number of oxytocin-immunoreactive cells detected in the BNSTmv compared to missense controls (F 1,28 =5.4,p=0.02,Fig. 1C, 1D).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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In the paper
“There was no evidence of neurotoxicity by morpholino treatment (supplementary fig.1B), consistent with previous reports (Reissner et al., 2012).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
What the sources say
- Not checked yetcites Reissner et al., 2012
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In the paper
“Planned comparisons revealed that vicarious defeat stress significantly increased vigilance in female (p<0.0001,d=1.9), but not male mice (p=0.1, d=1.4).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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In the paper
“The effects of stress on social vigilance were stronger in females than males (fig.2B, sex*stress interaction, F 1,36 =8.2, p=0.01).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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In the paper
“For social vigilance, effects of stress were blunted by antisense treatment (stress*treatment F 1,31 =6.2, p=0.02, fig.1F).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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In the paper
“About half (46% females, 43% males) of the Oxtr+ cells in the BNSTam co-expressed Gad1+ (fig.3J,K).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Venus positive fibers in the BNSTam originating from the BNSTmv were observed in both sexes, which further supported the hypothesis that the circuitry for social vigilance is intact in males and females.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
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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
“There were no effects of oxytocin injections placed outside the BNSTam (miss) on social approach or vigilance.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In females, treatment with oxytocin decreased social approach (F 3,21 =9.5, p<0.001, fig.4B).Compared to vehicle, both 0.2 ng (p=0.03,d=1.1) and 1.0 ng (p<0.001,d=4.8) infusions of oxytocin reduced social approach in a dose-dependent fashion.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Rests on an assumption: Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
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
“Interestingly, there were many fibers in the BNSTam, which is implicated as a key regulator of social anxietyrelated behavior.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“About 50% of Oxtr+ cells in the BNSTam coexpress Gad1+, suggesting that oxytocin may act on inhibitory neurons in the BNST as has been observed in the central nucleus of amygdala (Knobloch et al., 2012).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
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None of the sources cited for this claim have been checked yet.
In the paper
“Viral tracing experiments in males and females revealed fibers originating from oxytocin neurons within the BNST, anterior hypothalamus, and lateral hypothalamus, consistent with previous tracing experiments (Delville et al., 2000;Dong and Swanson, 2004) that were not celltype specific.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
What the sources say
- Not checked yetcites Delville et al., 2000
- Not checked yetcites Dong and Swanson, 2004
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In the paper
“Many Oxtr+ cells did not express Gad1+.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“There were no vGlut2 positive cells observed in the BNSTam, so Oxtr+/Gad1-cells may instead express Gad2 (Welch et al., 2019) or represent another type of neuronal or non-neuronal cells such as glia (Mittaud et al., 2002).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Social defeat reduced social approach and increased social vigilance in missense treated females but not antisense treated females.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
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In the paper
“Defeat reduced social approach and increased vigilance (J).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 8 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“Morpholino antisense reduced the number of oxytocin+ cells detected in BNSTmv compared to missense controls (n=5-10 per group).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 5- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Social defeat reduced social approach and increased social vigilance in missense treated females but not antisense treated females.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 6- 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.
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
“Defeat reduced social approach and increased vigilance (J).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 8 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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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
“Stress significantly increased oxytocin cell number in BNST, but not PVN.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 7 ·- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stress significantly increased oxytocin cell number in BNST, but not PVN.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plainn = 7- Asserted: passes — The authors put it forward as true.
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In the paper
“Oxytocin cell bodies in BNSTmv send projections to anteromedial BNST.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Defeat significantly increases vigilance behavior in females, but not males.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plainn = 10- Asserted: passes — The authors put it forward as true.
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In the paper
“Injections of antisense in the BNSTmv did not affect oxytocin cell numbers in the PVN.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Additional information
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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
“Oxytocin dose dependently reduced social approach, and only the high dose of oxytocin increased vigilance.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 5- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Defeat significantly increases vigilance behavior in females, but not males.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 10 ·- 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.
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
“Oxytocin reduced social approach and increased vigilance in males.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 6- 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.
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
“Oxytocin dose dependently reduced social approach, and only the high dose of oxytocin increased vigilance.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 5- 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.
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
“Oxytocin reduced social approach and increased vigilance in males.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 6- 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.
In the paper
“In female California mice, social defeat induces hyperactivity of oxytocin neurons in medioventral BNST (BNSTmv) up to 10 weeks after the last episode of social defeat (Steinman et al., 2016).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Introduction
What the sources say
- Not checked yetcites Steinman et al., 2016
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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 results show that a population of extra-hypothalamic oxytocin neurons play a key role in controlling stress-induced social anxiety behaviors.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Abstract
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Remarkably, social stress can induce both behavioral analogs in rodents (Duque-Wilckens et al., 2018;Newman et al., 2019), providing a unique opportunity to assess the neurobiological substrates underlying behavioral phenotypes associated with SAD.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Introduction
What the sources say
- Not checked yetcites Duque-Wilckens et al., 2018
- Not checked yetcites Newman et al., 2019
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.
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 results implicate oxytocin in the BNST as a potential modulator of social approach in males as well as females.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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.
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
“There were no effects of BNST antisense infusions on PVN oxytocin cells (supplementary fig.1F), indicating oxytocin knockdown in the BNST was site-specific.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The identification of fibers in the dorsal BNSTam was notable, as we previously showed that activation of oxytocin receptors in dorsal BNSTam is necessary for stress-induced social deficits in females (Duque-Wilckens et al., 2018).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
What the sources say
- Not checked yetcites Duque-Wilckens et al., 2018
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus, while oxytocin acting in hypothalamic-mesolimbic circuits promotes social approach (Dölen et al., 2013;Marlin et al., 2015;Song et al., 2016;Wang and Aragona, 2004;Williams et al., 2020), our data in the BNST support the hypothesis that divergent effects of oxytocin on social approach are mediated by discrete brain circuits (Grinevich et al., 2016;Shamay-Tsoory and Abu-Akel, 2016;Steinman et”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Introduction
What the sources say
- Not checked yetcites Grinevich et al., 2016
- Not checked yetcites Shamay-Tsoory and Abu-Akel, 2016
- Not checked yetcites Steinman et al., 2019
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data show that stress-induced synthesis of oxytocin in the BNST is necessary for stress-induced social deficits in female California mice.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“To our knowledge, this is the first demonstration that non-hypothalamic oxytocin synthesis can modulate behavior.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Together, our results suggest that the oxytocin-dependent circuit of social vigilance in the BNST is intact in both sexes, and that previously reported sex differences in behavioral responses to social stress (Duque-Wilckens et al., 2018;Trainor et al., 2011) are mediated by sex differences in the release of oxytocin.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
What the sources say
- Not checked yetcites Duque-Wilckens et al., 2018
- Not checked yetcites Trainor et al., 2011
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Social anxiety phenotypes are associated with increased activity in the BNSTam (Duque-Wilckens et al., 2018;Kollack-Walker et al., 1997;Markham et al., 2009), and pharmacological inhibition of oxytocin receptors in the BNSTam restores normative social approach behavior following social defeat (Duque-Wilckens et al., 2018).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
What the sources say
- Not checked yetcites Duque-Wilckens et al., 2018
- Not checked yetcites Kollack-Walker et al., 1997
- Not checked yetcites Markham et al., 2009
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results suggest that sex differences in stress-induced vigilance are mediated by sex-specific temporal activation and plasticity of oxytocinergic BNST neurons.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
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.
In the paper
“Social anxiety phenotypes are associated with increased activity in the BNSTam (Duque-Wilckens et al., 2018;Kollack-Walker et al., 1997;Markham et al., 2009), and pharmacological inhibition of oxytocin receptors in the BNSTam restores normative social approach behavior following social defeat (Duque-Wilckens et al., 2018).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
What the sources say
- Not checked yetcites Duque-Wilckens et al., 2018
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Although we do not know whether BNST oxytocin neurons synapse with neurons within these regions, there is evidence for non-synaptic, periaxonal or en passant release of oxytocin (Chini et al., 2017;Knobloch and Grinevich, 2014).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
What the sources say
- Not checked yetcites Chini et al., 2017
- Not checked yetcites Knobloch and Grinevich, 2014
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.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using antisense knockdown, we show that oxytocin synthesized in neurons within the BNST is necessary for stress-induced social vigilance and reduced social approach.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, our results suggest that the oxytocin-dependent circuit of social vigilance in the BNST is intact in both sexes, and that previously reported sex differences in behavioral responses to social stress (Duque-Wilckens et al., 2018;Trainor et al., 2011) are mediated by sex differences in the release of oxytocin.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
hedged- 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.
- Rests on an assumption: Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we outlined an oxytocinergic circuit within the BNST that is a critical hub driving stress-induced changes in social behavior.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 suggested that the behavioral function of the BNST oxytocinergic neural circuitry may be conserved between sexes.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, a nucleus containing only fibers of passage could receive oxytocin even in the absence of axon terminals.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Although the presence of oxytocin cells in the BNST has been described in multiple species (Caffé et al., 1989;DiBenedictis et al., 2017;Nasanbuyan et al., 2018), this is the first time that a behavioral function of these neurons has been demonstrated.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
What the sources say
- Not checked yetcites Caffé et al., 1989
- Not checked yetcites DiBenedictis et al., 2017
- Not checked yetcites Nasanbuyan et al., 2018
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results show that stress-induced intra-BNST oxytocin synthesis facilitates social anxiety-related behaviors.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Functional implications
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.
- Rests on an assumption: Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
In the paper
“Our results do not exclude a role of the PVN for inducing social vigilance, as volume diffusion of oxytocin through extracellular space or the ventricular system gives the PVN an extended reach (Landgraf and Neumann, 2004).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Functional implications
What the sources say
- Not checked yetcites Landgraf and Neumann, 2004
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 sum, data in multiple species support an important role of the BNST in social anxiety-related behaviors, and our work shows that oxytocin signaling may be a key underlying mechanism.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Functional implications
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.
- Rests on an assumption: Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
In the paper
“We previously found that at this moment, males show increased cFos/oxytocin colocalizations in the BNSTmv (Steinman et al., 2016).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
What the sources say
- Not checked yetcites Steinman et al., 2016
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 synthesis within BNSTmv is necessary for stress-induced increases in social vigilance and reduced social approach.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 5- 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.
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 infusion within BNSTam induces social vigilance in stress naïve females and males.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
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. 21
- Probably not a substantial claim. 11
- The quote only partly states this claim. 2
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
“Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Abstract
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.
- Rests on an assumption: Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
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
“There were no effects of defeat on approach behavior when the target mouse was absent (supplementary fig.2B) or in the open field (supplementary fig.2C, 2D).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Immunohistochemical analyses in the BNST (fig.3C) and the PVN (supplementary fig.3A) showed that on average, 63% of oxytocin-immunoreactive cells expressed Venus and that all Venus positive cells coexpressed oxytocin.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When stressed males were tested 10 min after a third episode of defeat (Fig. 1H), social approach was reduced (t 14 =2.46, p=0.02, d=1.23, fig.1I), and social vigilance was increased (t 14 =2.36, p=0.03, d=1.18, fig.1J) compared to naïve males.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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.
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
“There were no effects of stress or treatment on approach behavior during the acclimation phase when the target mouse was absent (supplementary fig.1C), or time spent in center (supplementary fig.1D) and distance traveled (supplementary fig.1D) during the open field phase.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stress increased social vigilance in missense treated females (p=0.03,d=0.96) but not antisense treated females.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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.
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
“Importantly, vicarious stress increased the number of oxytocin cells in the BNST (t 14 =2.721, p=0.01, d=1.4,fig 2D), but not in the PVN (fig.2E), comparable to what was previously reported in female California mice.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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.
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
“Defeat reduced social approach in females receiving missense (p=0.02,d=1.1), but not in females receiving antisense.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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
“Social stress increases oxytocin cell mRNA and counts in the BNST of female California mice (Steinman et al., 2016) and C57BL6/J mice.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
What the sources say
- Not checked yetcites Steinman et al., 2016
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that comparable to females, stressed male California mice show reduced social approach and increased social vigilance at this time point.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
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.
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
“Similarly, oxytocin also increased social vigilance (F 2,21 =5.3, p=0.01, fig.4E), with 1.0 ng of oxytocin increasing vigilance compared to vehicle (p<0.001,d=1.27).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
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.
- Rests on an assumption: Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
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
“Treatment with oxytocin also increased social vigilance in females (F 3,21 =8.8, p=0.001, fig.4C).The 1.0 ng (p<0.001,d=2.3) but not the 0.2 ng dose increased vigilance in stress naïve females compared to vehicle.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
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.
- Rests on an assumption: Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In males, oxytocin also reduced social approach (F 2,21 =6.7, p=0.00), with 1.0 ng of oxytocin reducing social approach compared to vehicle (p=0.00,d=1.93 fig.4D).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
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.
- Rests on an assumption: Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found no vGlut2+ cells in the BNSTam, although there were vGlut2+ cells in the adjacent lateral septum (supplementary fig.3B).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stress increased BNSTmv oxytocin cell number in animals receiving missense, but this was prevented by injections of morpholino missense.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
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.
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
“There were no differences in cycle thresholds between groups for B2m.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Additional information
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A 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
“No effects of stress or sex were found.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plainn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Social defeat did not affect approach, time in center, or distance traveled when there was no social target present.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Additional information
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“No Glut+ cells were found in the BNSTam, but there were Glut+ cells in the adjacent lateral septum.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Additional information
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A 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
“There were no effects of antisense injections on approach, time spent in center, or distance traveled when no social target was present.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Additional information
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“No Glut+ cells were found in the BNSTam, but there were Glut+ cells in the adjacent lateral septum.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Additional information
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus, while oxytocin acting in hypothalamic-mesolimbic circuits promotes social approach (Dölen et al., 2013;Marlin et al., 2015;Song et al., 2016;Wang and Aragona, 2004;Williams et al., 2020), our data in the BNST support the hypothesis that divergent effects of oxytocin on social approach are mediated by discrete brain circuits (Grinevich et al., 2016;Shamay-Tsoory and Abu-Akel, 2016;Steinman et”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Introduction
What the sources say
- Not checked yetcites Dölen et al., 2013
- Not checked yetcites Marlin et al., 2015
- Not checked yetcites Song et al., 2016
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data suggest that stress-sensitive oxytocin neurons located in the BNSTmv project to the BNSTam, where oxytocin acts to drive a social anxiety-related phenotype.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Discussion
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.
- Rests on an assumption: Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
In the paper
“Female mice were randomly assigned to control handling or vicarious social defeat stress as described previously (Iñiguez et al., 2018).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
What the sources say
- Not checked yetcites Iñiguez et al., 2018
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“However, the key role of BNST oxytocin neurons play in long term changes in female-biased social avoidance and vigilance suggests that these cells may be related to symptoms associated with social anxiety disorder (Asher et al., 2017) and depression (Kessler et al., 2005), which are more common in women than men.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Functional implications
What the sources say
- Not checked yetcites Asher et al., 2017
- Not checked yetcites Kessler et al., 2005
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“About 50% of Oxtr+ cells in the BNSTam coexpress Gad1+, suggesting that oxytocin may act on inhibitory neurons in the BNST as has been observed in the central nucleus of amygdala (Knobloch et al., 2012).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin produced by BNST neurons promotes social vigilance and reduces social approach
What the sources say
- Not checked yetcites Knobloch et al., 2012
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
“Mice were randomly assigned to control handling or social defeat for 3 consecutive days as described previously (Trainor et al., 2011).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
What the sources say
- Not checked yetcites Trainor et al., 2011
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.
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
“One week after the last episode of control handling or social defeat, animals were randomly assigned to receive one bilateral 0.2uL injection of 100pM morpholino missense or antisense aimed a little anterior to medioventral BNST (BNSTmv, AP:0.39,ML: 1.1, DV:-5.85).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
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
“Vigilance behavior, defined as time spent with head oriented toward the target mouse while outside of the interaction zone, was manually analyzed by an observer blind to treatment.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
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.
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 test whether stressinduced increases in oxytocin synthesis within the BNSTmv are necessary for stress-induced social deficits, females were first randomly assigned to social defeat or control conditions (Fig. 1B).”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
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.
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
“After 7 days, mice were randomly assigned to receive bilateral 200nl infusions of either aCSF, 0.2ng (females only), or 1ng (males and females) of oxytocin using internal guides that projected 1 mm past the guides.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The quote only partly states this 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
“In Mus musculus, vicarious social stress increases social vigilance and BNST OT cell number in females.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
plaindirectn = 10 ·- 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.
Exogenous oxytocin infused into BNSTam acts through oxytocin receptors to produce its effects on social behavior.
“Next, we tested whether administration of oxytocin within the BNSTam is sufficient to reduce social approach and increase vigilance in stress naïve females and males (fig.4A).”
The paper relies on this without support.
Morpholino oligos inhibit protein synthesis by blocking the translation initiation complex.
“Morpholino oligos inhibit protein synthesis by blocking the translation initiation complex.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“In female California mice, SDS resulted in reduced social approach and increased social vigilance along with increased Oxt mRNA levels and co-localization of OXT with c-fos (a marker of cellular activity) in the bed nucleus of the stria ter minalis (BNST) (Duque-Wilckens et al., 2020).”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Duque-Wilckens et al., 2020
The cited source says what the claim attributes to it.
In the citing paper
“Interestingly, knocking down OXT in the BNST prevented the SDS-induced increase in social vigilance and decrease in social approach, while OXT infusion into the BNST induced social vigilance in both stress-naïve female and male California mice”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Duque-Wilckens et al., 2020
The cited source says what the claim attributes to it.
In the citing paper
“Previous work in California mice (Peromyscus californicus) shows that social defeat stress has stronger effects on BNST structure and function in adult females than males (37, 38) and that these changes drive stress-induced social avoidance and social vigilance (39–41).”
From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [39]
In the citing paper
“However, OXT neurons in the BNST of California mice make local connections within the BNST, project to the hypothalamus, and are involved in social vigilance (66).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [66]
In the citing paper
“However, in California mice, knockdown of OXT or administration of OXTR antagonist in the anterior BNST increased social approach and decreased social vigilance, an anxiety-like behavior, which suggests that OXT may also drive social anxiety-like behavior depending on its source or context (66, 88).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [66]
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 major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
“one bilateral 0.2uL injection of 100pM morpholino missense or antisense”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Additional information
“one bilateral 100pmol morpholino injections within BNSTmv”
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
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
“Stress increased BNSTmv oxytocin cell number in animals receiving missense, but this was prevented by injections of morpholino missense.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
“An alternate schedule of multiple injections of a lower dose of morpholino antisense also reduced oxytocin cell number in the BNSTmv (stress missense vs. stress antisense p=0.01, d=1.16, supplementary fig.1H,1I).”
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
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
“All behavioral and brain tissue analyses were conducted two weeks after the last episode of social defeat.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
“When stressed males were tested 10 min after a third episode of defeat (Fig. 1H)”
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
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Results
“vicarious stress increased the number of oxytocin cells in the BNST (t 14 =2.721, p=0.01, d=1.4,fig 2D)”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
“D,E.Effects of vicarious defeat stress on oxytocin cell number (n=7 per group).”
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
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Experiments in California mice
“J,K.Circle chart representing percentage of Oxt +/Gad+ cells present in the BNSTam of males and females.”
§ Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance > Oxytocin cells in the BNSTmv project to the anteromedial BNST
“About half (46% females, 43% males) of the Oxtr+ cells in the BNSTam co-expressed Gad1+ (fig.3J,K).”
Citations
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Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.593 · Cited by 20,391
Diagnostic and Statistical Manual of Mental Disorders(DSM)
Leong, F. T. L. (2008) · Sage eBooks · doi:10.4135/9781412963978.n182 · Cited by 10,861
Neurotrophin regulation of neural circuit development and function
Park, H., & Poo, M.-M. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3379 · Cited by 2,060
Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans
Kirsch, P., Esslinger, C., Chen, Q., Mier, D., Lis, S., Siddhanti, S., Gruppe, H., Mattay, V. S., Gallhofer, B., & Meyer-Lindenberg, A. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3984-05.2005 · Cited by 1,639
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
Binder (2004) · doi:10.1080/08977190410001723308 · Cited by 1,481
Social Phobia: Diagnosis, Assessment, and Treatment
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Single-Cell Multi-omic Integration Compares and Contrasts Features of Brain Cell Identity
Welch, J. D., Kozareva, V., Ferreira, A., Vanderburg, C., Martin, C., & Macosko, E. Z. (2019) · Cell · doi:10.1016/j.cell.2019.05.006 · Cited by 1,193
Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin
Dölen, G., Darvishzadeh, A., Huang, K. W., & Malenka, R. C. (2013) · Nature · doi:10.1038/nature12518 · Cited by 1,161
Research works printed but not linked: 1
- J. Wahis Oxytocin acts on astrocytes in the central amygdala to promote a positive emotional state. bioRxiv :2020.02.25.963884 (2020). Posted 26 February 2020.
Cited by
Sorted by citations
Sex differences in anxiety and depression: circuits and mechanisms
Bangasser, D. A., & Cuarenta, A. (2021) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00513-0 · Cited by 479
Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities
Rigney, N., de Vries, G. J., Petrulis, A., & Young, L. J. (2022) · Endocrinology · doi:10.1210/endocr/bqac111 · Cited by 191
Neural circuits of social behaviors: Innate yet flexible
Wei, D., Talwar, V., & Lin, D. (2021) · Neuron · doi:10.1016/j.neuron.2021.02.012 · Cited by 199
Roles of Oxytocin in Stress Responses, Allostasis and Resilience
Takayanagi, Y., & Onaka, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010150 · Cited by 173
Detection, processing and reinforcement of social cues: regulation by the oxytocin system
Menon, R., & Neumann, I. D. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00759-w · Cited by 100
Metadata
- Authors
- Duque-Wilckens, N., Torres, L. Y., Yokoyama, S., Minie, V. A., Tran, A. M., Petkova, S. P., Hao, R., Ramos-Maciel, S., Rios, R. A., Jackson, K., Flores-Ramirez, F. J., Garcia-Carachure, I., Pesavento, P. A., Iñiguez, S. D., Grinevich, V., & Trainor, B. C.
- Affiliations
- Department of Psychology, University of California, Davis, CA 95616;
- University of California, Davis (US)
- Department of Psychology, The University of Texas at El Paso, El Paso, TX 79902;
- The University of Texas at El Paso (US)
- Heidelberg University (DE)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-10-05
- Volume
- 117
- Issue
- 42
- Pages
- 26406-26413
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7585015
- OpenAlex
- W3091710413
- Cited by
- 139
- References
- 86
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 17 · 2023: 20 · 2022: 17 · 2021: 29 · 2020: 6
- FWCI
- 19.70
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (R01 MH121829-01)
- HHS | NIH | National Institute of General Medical Sciences (SC3GM130467)
- Deutsche Forschungsgemeinschaft (Collaborative Research Center (SFB) 1158, GR 3619/701, GR 3619/4-1)
- SFB (1158)
- SNSF-DFG (GR 3619/8-1)
- Fritz Thyssen Stiftung (10.16.2.018 MN)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- oxytocin neurons, social stress, social vigilance, social avoidance, social anxiety, lateral hypothalamus, anterior hypothalamus, viral tracing, defensive behavior
- MeSH terms
- Animals, Anxiety, Avoidance Learning, Brain, Brain Mapping, Female, Hypothalamus, Male, Neurons, Oxytocin, Peromyscus, Septal Nuclei, Social Behavior, Stress, Psychological, Receptors, Oxytocin, Mice
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