Oxytocin receptors modulate a social salience neural network in male prairie voles
Open accessAbstract
&NA; Social behavior is regulated by conserved neural networks across vertebrates. Variation in the organization of neuropeptide systems across these networks is thought to contribute to individual and species diversity in network function during social contexts. For example, oxytocin (OT) is an ancient neuropeptide that binds to OT receptors (OTRs) in the brain and modulates social and reproductive behavior across vertebrate species, including humans. Central OTRs exhibit extraordinarily diverse expression patterns that are associated with individual and species differences in social behavior. In voles, OTR density in the nucleus accumbens (NAc)—a region important for social and reward learning—is associated with individual and species variation in social attachment behavior. Here we test whether OTRs in the NAc modulate a social salience network (SSN)—a network of interconnected brain nuclei thought to encode valence and incentive salience of sociosensory cues—during a social context in the socially monogamous male prairie vole. Using a selective OTR antagonist, we test whether activation of OTRs in the NAc during sociosexual interaction and mating modulates expression of the immediate early gene product Fos across nuclei of the SSN. We show that blockade of endogenous OTR signaling in the NAc during sociosexual interaction and mating does not strongly modulate levels of Fos expression in individual nodes of the network, but strongly modulates patterns of correlated Fos expression between the NAc and other SSN nuclei. HighlightsOxytocin receptor (OTR) signaling in NAc does not modulate male mating behavior.Mating induces Fos‐ir across a social salience network (SSN).During mating, Fos‐ir across SSN nuclei is correlated with Fos‐ir in the NAc shell.Blocking accumbal OTRs decouples the NAc shell from the SSN. Graphical abstract Figure. No caption available.
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Written from the paper’s full text.
TL;DR
Site-specific blockade of oxytocin receptors (OTRs) in the nucleus accumbens (NAc) of male prairie voles did not strongly alter Fos expression in individual social salience network (SSN) nuclei during sociosexual interaction and mating, but it strongly disrupted correlated Fos expression between the NAc shell and other SSN nodes. The authors conclude that endogenous accumbal OTR signaling modulates distributed network coupling rather than uniform regional activity.
Key findings
- OTR antagonist (OTA) in the NAc did not significantly change Fos-ir across brain regions among mated males (aCSF-mated vs OTA-mated: t1,20 = 0.87, p = 0.39), while mating itself increased Fos-ir across the SSN (t1,25 = 4.49, p < 0.001), in all analyzed nuclei except the VTA.
- OTA strongly reduced correlated Fos-ir between the NAc shell and other SSN nuclei: non-accumbal SSN Fos-ir explained R² = 0.91 of NAc shell Fos-ir variance in aCSF-treated animals versus R² = 0.20 in OTA-treated animals (71% difference, permutation p = 0.02); residual variance was greater in OTA- (σ² = 0.82) than aCSF-treated subjects (σ² = 0.05; F1,20 = 17.25, p < 0.001).
- Global covariance across the SSN did not differ by treatment: first principal component variance explained differed by <0.01 (p = 0.98).
- NAc OTA did not alter mating frequency (aCSF: 4.11 ± 1.05 intromission bouts/30 min; OTA: 5.56 ± 1.19; z = 1.328, p = 0.184) or analyzed sociosexual behaviors among mated animals (treatment effect F1,109 ≤ 0.01, p > 0.99, Eta-squared < 0.01). A non-significant trend suggested increased NAc shell Fos-ir in OTA-treated subjects (t1,20 = 1.85, p = 0.08).
Methods
- Sexually naïve adult male prairie voles received bilateral cannulation targeting the dorsal NAc shell, then microinjection of either 500 nL aCSF or 2.5 ng/μL OTA 3 h before a 30-min video-recorded cohabitation with a sexually experienced, ovariectomized, estrogen-primed adult female; unexposed controls had cage/bedding disturbance without a female.
- Fos immunohistochemistry was quantified in seven SSN nuclei: NAc shell, anterior olfactory nucleus, prefrontal cortex, paraventricular nucleus of the hypothalamus, medial amygdala, basolateral amygdala, and ventral tegmental area. Fos analyses were restricted to subjects that mated (aCSF n = 11; OTA n = 12); behavioral analyses included aCSF n = 13, OTA n = 15, and aCSF-unexposed n = 5.
- Analyses used linear mixed-effects models with immunohistochemistry batch and subject ID as random effects, two-way repeated-measures ANOVA and Poisson regression for behavior, and multiple linear regression, PCA, and permutation testing for Fos covariance.
Limitations
- The paper states that the neuronal phenotypes and anatomical projections of Fos-positive neurons in each SSN nucleus are unknown; that site-specific OTA targets all region-specific OTRs, obscuring roles dependent on neuronal phenotype and cellular localization; that experiments focused on OTRs in a single SSN nucleus in male prairie voles, so future work is needed on other systems, brain areas, female subjects, behavioral contexts, and species; and that site-specific OTR blockade likely does not reflect natural intra- and interspecific variation in OTR expression and signaling.
- The text also notes that locomotion per se could not be directly analyzed, although the authors argue active behaviors did not differ between treatment groups.
- Evident from the text: Fos covariance is correlational and cannot establish causal direction; the unexposed control group was small (n = 5); and Fos analyses excluded non-mated subjects, limiting generalizability.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Claims the paper makes
0 of 54 cited sources checked · 0 supported · 0 flagged
- Findingown data
Fos-ir did not significantly differ between aCSF-mated and OTA-mated animals across brain regions.
“This test showed that Fos-ir did not significantly differ between aCSF-mated and OTA-mated animals across brain regions (t1,20 = 0.87, p = 0.39).”
Quote in the paperSubstantial claim - Findingown data
Sociosexual interaction and mating with the stimulus female was associated with increased Fos-ir across SSN nuclei in the present experiments.
“These analyses revealed significantly increased Fos-ir in aCSF-mated (t2,24 = 3.74, p = 0.001) and OTA-mated (t2,24 = 4.47, p < 0.001) subjects compared to unexposed controls.”
Quote in the paperSubstantial claim - Findingown data
Blockade of endogenous OTR signaling in the NAc during sociosexual interaction and mating does not strongly modulate levels of Fos expression in individual nodes of the SSN.
“We show that blockade of endogenous OTR signaling in the NAc during sociosexual interaction and mating does not strongly modulate levels of Fos expression in individual nodes of the network”
Quote in the paperSubstantial claim- The authors state this as an assumption: The SSN is a neural network that modulates selective social attachment and other forms of associative social learning by attaching valence and incentive salience to sociosensory cues.
- Findingown data
aCSF-treated males engaged in an average frequency of 4.11 ± 1.05 intromission bouts per 30 min with the stimulus female compared to 5.56 ± 1.19 bouts per 30 min in OTA-treated males.
“aCSF-treated males (n = 13) engaged in an average frequency of 4.11 ± 1.05 intro-mission bouts per 30 min with the stimulus female compared to 5.56 ± 1.19 bouts per 30 min in OTA-treated males (n = 15).”
Quote in the paperSubstantial claim - Findingown data
Among mated animals, OTA versus aCSF treatment had no detectable effect on any of the analyzed sociosexual behaviors.
“Thus, among mated animals, OTA versus aCSF treatment had no detectable effect on any of the analyzed sociosexual behaviors”
Quote in the paperSubstantial claim
- Findingown data
Blockade of endogenous OTR signaling in the NAc during sociosexual interaction and mating strongly modulates patterns of correlated Fos expression between the NAc and other SSN nuclei.
“but strongly modulates patterns of correlated Fos expression between the NAc and other SSN nuclei.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The SSN is a neural network that modulates selective social attachment and other forms of associative social learning by attaching valence and incentive salience to sociosensory cues.
- Findingown data
There were no significant differences in mating frequency between OTA- and aCSF-treated subjects (z = 1.328; p = 0.184).
“A regression analysis comparing Poisson distributions of mating bouts showed no significant differences in mating frequency between OTA- and aCSF-treated subjects (z = 1.328; p = 0.184)”
Quote in the paperSubstantial claim - Findingown data
The difference in variance explained (71%) between aCSF and OTA groups was statistically significant (p = 0.02).
“In support of our hypothesis, permutation testing indicated that this difference in variance explained (71%) was statistically significant (p = 0.02).”
Quote in the paperSubstantial claim- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Findingown data
The variance of MLR residuals was significantly greater in OTA-treated (σ2 = 0.82) than aCSF-treated (σ2 = 0.05) subjects.
“In further support of our hypothesis, the variance of MLR residuals was significantly greater in OTA- (σ2 = 0.82) compared to aCSF- (σ2 = 0.05) treated subjects (F-test; F1,20 = 17.25, p < 0.001; Fig. 2B).”
- Also stated in: § 4. Discussion · hedged
“In further support of our hypothesis, we found that the variance of residuals extracted from the MLR model was significantly greater among OTA-treated compared to aCSF-treated subjects, indicating that observed Fos-ir count values deviated further from MLR-predicted Fos-ir count values in OTA- compared to aCSF-treated subjects.”
Quote in the paperSubstantial claim- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Also stated in: § 4. Discussion · hedged
- Findingown data
In aCSF-treated animals, Fos-ir in non-accumbal SSN nodes explained 91% of the variance in NAc shell Fos-ir, whereas in OTA-treated animals it explained 20%.
“Consistent with this hypothesis, a MLR model fitting Fos-ir count in the NAc shell against Fos-ir count in every other SSN node revealed that Fos-ir count in non-accumbal SSN nodes explained a large amount of the variance in Fos-ir count in the NAc shell in aCSF-treated animals (R2 = 0.91) but not in animals treated with OTA (R2 = 0.20).”
- Also stated in: § 4. Discussion · boosted
“In support of this hypothesis, we observed a robust and significant effect of treatment on correlated Fos-ir between the NAc shell and other SSN nuclei; Fos-ir counts in non-accumbal SSN nuclei collectively explained the vast majority of variance of Fos-ir counts in the NAc shell in aCSF-treated (91% of variance explained) but not OTA-treated (20% of variance explained) subjects.”
Quote in the paperSubstantial claim- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Also stated in: § 4. Discussion · boosted
- Findingown data
There was no effect of OTA treatment in the NAc on global covariance of Fos-ir across the SSN; the variance explained by the first principal component was virtually identical in OTA- and aCSF-treated animals (difference in R2 < 0.01, p = 0.98).
“In line with our hypothesis, we found no effect of treatment on global covariance of Fos-ir across the SSN; the variance explained by the first principal component was virtually identical in animals treated with OTA and aCSF (difference in R2 < 0.01, p = 0.98).”
- Also stated in: § 4. Discussion · hedged
“The effect of treatment on correlated Fos-ir across SSN nuclei was not general-izable to the network as a whole, as PCA combined with permutation testing suggested that global patterns of covariance of Fos-ir across the SSN did not differ between aCSF- and OTA-treated subjects.”
- Also stated in: § 4. Discussion · boosted
“In contrast to previous experiments following central OTR blockade, here we show that site-specific blockade of OTRs in the NAc during sociosexual interaction does not modulate global patterns of correlated Fos-ir across nodes of the SSN.”
Quote in the paperSubstantial claim- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Also stated in: § 4. Discussion · hedged
- Findingown data
Sociosexual interaction and mating with a female was associated with a significant increase in Fos-ir across the SSN.
“This test confirmed that sociosexual interaction and mating with a female was associated with a significant increase in Fos-ir across the SSN (t1,25 = 4.49, p < 0.001), consistent with previous results (Johnson et al., 2016).”
- Also stated in: § 4. Discussion · boosted
“Fos-ir across SSN nuclei was significantly higher in mated versus un-exposed subjects, regardless of OTA- versus aCSF-treatment, confirming that sociosexual interaction and mating was associated with a robust induction of Fos-ir across the network.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Johnson et al., 2016 source
Not checked in the free run.
- Also stated in: § 4. Discussion · boosted
- Findingown data
Site-specific OTR blockade in the NAc had no effect on mating frequency or any of the analyzed sociosexual behaviors in male prairie voles during 30 min of sociosexual interaction with a female.
“Site-specific blockade of OTRs in the NAc had no effect on mating frequency or any of the analyzed sociosexual behaviors in male prairie voles during 30 min of sociosexual interaction with a female.”
Quote in the paperSubstantial claim- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Findingown data
There were no region-specific differences in Fos-ir distinguishing aCSF-treated versus OTA-treated animals.
“This pattern was observed in all brain regions analyzed, with no region-specific differences in Fos-ir distinguishing aCSF-treated versus OTA-treated animals.”
Quote in the paperSubstantial claim- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Findingown data
In mated animals, OTA treatment in the NAc shell was associated with a non-significant trend toward increased Fos-ir compared to aCSF treatment.
“This analysis revealed a trend toward increased Fos-ir in OTA-treated compared to aCSF-treated subjects, although this trend was not statistically significant (t1,20 = 1.85, p = 0.08).”
- Also stated in: § 4. Discussion · plain
“Notably, however, we observed a statistical trend toward increased Fos-ir in OTA-treated versus aCSF-treated subjects in the NAc shell, similar to previous results following ICV administration of OTA (Johnson et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Johnson et al., 2016 source
Not checked in the free run.
- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Also stated in: § 4. Discussion · plain
- Findingown data
Sociosexual interaction and mating with a female was associated with a significant increase in Fos-ir in all analyzed SSN nuclei except the VTA.
“These analyses confirmed that sociosexual interaction and mating with a female was associated with a significant (p < 0.05) increase in Fos-ir in all analyzed SSN nuclei with the exception of the VTA (Fig. 2A; Supplementary Table 1).”
Quote in the paperSubstantial claim - Interpretationcitation
Evolutionary plasticity in region-specific OTR expression is a deeply conserved mechanism contributing to social behavioral diversity within and across species.
“Together these data suggest that evolutionary plasticity in region-specific OTR expression is a deeply conserved mechanism contributing to social behavioral diversity within and across species.”
Quote in the paperNot a substantial claim - Premiseown data
Endogenous central OTR signaling during sociosexual interaction strongly modulates patterns of correlated Fos-ir across SSN nuclei.
“but strongly modulates patterns of correlated Fos-ir across SSN nuclei”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Johnson et al., 2016 source
Not checked in the free run.
- The authors state this as an assumption: The SSN is a neural network that modulates selective social attachment and other forms of associative social learning by attaching valence and incentive salience to sociosensory cues.
- Premisecitation
Previous experiments did not address the functional roles of region-specific OTR populations.
“These experiments, however, did not address the functional roles of region-specific OTR populations.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Johnson et al., 2016 source
Not checked in the free run.
- Premisecitation
OTR densities in the NAc correlate with socially monogamous mating strategies and other forms of social behavioral variation in prairie voles and other mammals.
“OTR densities in the NAc correlate with socially monogamous mating strategies and other forms of social behavioral variation in prairie voles and other mammals”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Blockade of endogenous OTR (and other neuromodulatory receptor) signaling in the NAc inhibits pair bond formation and other forms of social behavior in prairie voles and other rodents.
“blockade of endogenous OTR (and other neuromodulatory receptor) signaling in the NAc inhibits pair bond formation and other forms of social behavior in prairie voles and other rodents”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Endogenous central OTR signaling during sociosexual interaction does not strongly modulate levels of Fos-immunoreactivity (Fos-ir) within individual SSN nuclei.
“We previously found that endogenous central OTR signaling during sociosexual interaction does not strongly modulate levels of Fos-immunoreactivity (Fos-ir) within individual SSN nuclei”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Johnson et al., 2016 source
Not checked in the free run.
- The authors state this as an assumption: The SSN is a neural network that modulates selective social attachment and other forms of associative social learning by attaching valence and incentive salience to sociosensory cues.
- Premisecitation
In voles, OTR density in the nucleus accumbens (NAc) is associated with individual and species variation in social attachment behavior.
“In voles, OTR density in the nucleus accumbens (NAc)—a region important for social and reward learning—is associated with individual and species variation in social attachment behavior.”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
In humans, intranasal OT administration to romantically attached males modulates BOLD responses in the NAc during viewing of a partner's face.
“In humans, intranasal OT administration to romantically attached males modulates BOLD responses in the NAc during viewing of a partner's face”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Scheele et al., 2013 source
Not checked in the free run.
- Interpretationown data
OTRs in other nuclei modulate mating frequency in male prairie voles.
“suggesting that OTRs in other nuclei modulate mating frequency in male prairie voles.”
Quote in the paperSubstantial claim - Interpretationown data
Any observed differences in Fos-ir between OTA- and aCSF-treated subjects in these experiments were not due to differences in performance of the analyzed social behaviors.
“Importantly, these data suggest that any observed differences in Fos-ir between OTA- and aCSF-treated subjects in these experiments were not due to differences in performance of the analyzed social behaviors.”
Quote in the paperSubstantial claim - Interpretationown data
Any significant differences in Fos-ir between treatment groups are not due to differences in any of the analyzed sociosexual behaviors.
“Importantly, these results suggest that any significant differences in Fos-ir between treatment groups are not due to differences in any of the analyzed sociosexual behaviors.”
Quote in the paperSubstantial claim - Premisecitation
Intranasal OT administration modulates correlated fluctuations in BOLD responses across limbic, striatal, cortical, and/or brainstem nuclei during a variety of social contexts in rhesus macaques and humans.
“For example, fMRI experiments in both rhesus macaques and humans have found that intranasal OT administration modulates correlated fluctuations in BOLD responses across limbic, striatal, cortical, and/or brainstem nuclei during a variety of social contexts (Bethlehem et al., 2013; Gorka et al., 2015; Kirsch et al., 2005; Liu et al., 2015; Riem et al., 2012; Rilling et al., 2012).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationown data
These are the first data to demonstrate that endogenous activation of a region-specific neuropeptide receptor population modulates distributed patterns of transcriptional activity across a neural network in a behaving vertebrate.
“To our knowledge these are the first data to demonstrate that endogenous activation of a region-specific neuropeptide receptor population modulates distributed patterns of transcriptional activity across a neural network in a behaving vertebrate, linking OTR populations that are critical for social behavior with network properties that are hypothesized to be critical for social information proces”
Quote in the paperSubstantial claim - Interpretationown data
Activation of accumbal OTRs selectively modulates coupling of the NAc shell with other SSN nodes.
“Instead, these data support the view that activation of accumbal OTRs selectively modulates coupling of the NAc shell with other SSN nodes.”
Quote in the paperSubstantial claim- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Rests on an assumption: Correlated Fos-ir between brain regions reflects functional coupling between neuronal populations.
- Study design and conductreasoning
Site-specific OTA administration targets all region-specific OTRs, obscuring distinct functional roles that may depend on neuronal phenotype and cellular localization.
“Secondly, site-specific OTA administration targets all region-specific OTRs, obscuring any distinct functional roles that may depend on neuronal phenotype and cellular localization; future electrophysiological investigations are necessary to dissect the neuromodulatory roles of OTRs in different cellular contexts.”
Quote in the paperNot a substantial claim - Interpretationown data
Endogenous accumbal OTR signaling during sociosexual interaction and mating robustly modulates how synaptic plasticity and transcriptional activity in the NAc shell are correlated with synaptic plasticity and transcriptional activity in other nodes of the SSN.
“Taken together these data provide strong evidence that endogenous accumbal OTR signaling during sociosexual interaction and mating robustly modulates how synaptic plasticity and transcriptional activity in the NAc shell are correlated with synaptic plasticity and transcriptional activity in other nodes of the SSN.”
Quote in the paperSubstantial claim- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Rests on an assumption: Correlated Fos-ir between brain regions reflects functional coupling between neuronal populations.
- Premisecitation
ICV administration of OTA reduces mating frequency in male prairie voles.
“We previously demonstrated that ICV administration of OTA reduces mating frequency in male prairie voles (Johnson et al., 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Johnson et al., 2016 source
Not checked in the free run.
- Interpretationreasoning
It is unlikely that differences in Fos-ir between treatment groups are accounted for by differences in movement during the cohabitation.
“Additionally, because most of the analyzed behaviors are active behaviors, it is unlikely that differences in Fos-ir between treatment groups are accounted for by differences in movement during the cohabitation, although we could not directly analyze locomotion per se.”
Quote in the paperSubstantial claim - Interpretationreasoning
OTRs in other nuclei modulate sexual behavior in male prairie voles.
“Taken together, these data suggest that OTRs in other nuclei modulate sexual behavior in male prairie voles, consistent with findings in rats (Argiolas and Melis, 2013; Gil et al., 2011).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Argiolas and Melis, 2013
Not checked in the free run.
- cites Gil et al., 2011 source
Not checked in the free run.
- Rests on an assumption: OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
- Study design and conductcitation
Site-specific OTR blockade does not likely reflect natural intra- and interspecific variation in levels of region-specific OTR expression and signaling.
“Finally, site-specific OTR blockade does not likely reflect natural intra- and interspecific variation in levels of region-specific OTR expression and signaling (King et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites King et al., 2016 source
Not checked in the free run.
- May combine two claims. 11
- Classified as probably not a substantial claim. 21
- The quote only partly states this claim. 1
May combine two claims.
PremisecitationThe NAc is anatomically positioned as an integration hub within the SSN, receiving direct projections from every other SSN nucleus except the AON, including direct OTergic axonal projections from the PVN.
“The NAc is anatomically positioned as an integration hub within the SSN, receiving direct projections from every other SSN nucleus—with the exception of the AON—including direct OTergic axonal projections from the PVN”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Ross et al., 2009a
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe social decision-making network (SDMN) is thought to modulate social communication, parenting, sexual, and aggressive behaviors across vertebrates.
“the social decision-making network (SDMN) represents a synthesis of previously described social behavior and mesolimbic reward networks, and is thought to modulate social communication, parenting, sexual, and aggressive behaviors across vertebrates”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Goodson, 2005 source
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- cites O'Connell and Hofmann, 2011, 2012
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Probably not a substantial claim: may not pass S1 (asserted).
PremisecitationOrganizational plasticity of steroid hormone and neuropeptide systems across the SDMN is an important mechanism contributing to diversity in distributed network function and social behavior within and across species.
“It is further hypothesized that organizational plasticity of steroid hormone and neuropeptide systems across the SDMN is an important mechanism contributing to diversity in distributed network function and social behavior within and across species”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationThe NAc is an SSN and SDMN nucleus in which OTRs (or homologous OT-like receptors) are variably expressed across distant vertebrate lineages.
“Briefly, the NAc is a SSN (and SDMN) nucleus in which OTRs (or homologous OT-like receptors) are variably expressed across distant vertebrate lineages”
Quote in the paperSubstantial claim0 of 1 sources checked- cites O'Connell and Hofmann, 2012
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCritical functional roles of central and region-specific OTR populations in modulating social behavior have been demonstrated using selective OTR antagonists (OTAs), viral vector-mediated gene transfer, and/or RNAi knockdown in fishes, birds, and mammals.
“The critical functional roles of central and region-specific OTR populations in modulating social behavior have been demonstrated using selective OTR antagonists (OTAs), viral vector-mediated gene transfer, and/or RNAi knockdown in fishes”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Goodson and Bass, 2000
Not checked in the free run.
- cites Goodson et al., 2009
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- cites Bosch and Neumann, 2012
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationCentral OTRs exhibit extraordinarily diverse expression patterns that are associated with individual and species differences in social behavior.
“Central OTRs exhibit extraordinarily diverse expression patterns that are associated with individual and species differences in social behavior.”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCentral distribution patterns and region-specific densities of OTRs have undergone rapid evolutionary divergence between closely related species of birds and mammals that exhibit divergent social behavior.
“Central distribution patterns and region-specific densities of OT receptors (OTRs) have undergone rapid evolutionary divergence between closely related species of birds and mammals that exhibit divergent social behavior”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrevious experiments in non-mammalian species have used correlated expression of cytochrome oxidase and immediate early genes (IEGs) to demonstrate that distributed patterns of transcriptional and metabolic activity across SDMN nuclei are strongly predictive of social context and behavior.
“Previous experiments in non-mammalian species have used correlated expression of cytochrome oxidase (a metabolic marker) and immediate early genes (IEGs) to demonstrate that distributed patterns of transcriptional and metabolic activity across SDMN nuclei are strongly predictive of social context and behavior”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOT is a highly conserved neuropeptide that modulates reproductive physiology and behavior across bilaterian animals, including nematode worms, rodents, and humans.
“OT is a highly conserved neuro-peptide that modulates reproductive physiology and behavior across bilaterian animals, including nematode worms, rodents, and humans”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S1 (asserted).
PremisecitationDistributed patterns of activity across the network more strongly reflect social context and behavior than activity within individual brain regions.
“It is explicitly hypothesized that distributed patterns of activity across the network more strongly reflect social context and behavior than activity within individual brain regions.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Goodson and Kabelik, 2009
Not checked in the free run.
May combine two claims.
PremisecitationOXTR polymorphisms in the prairie vole robustly predict individual differences in OTR density in the NAc as well as pair bonding behavior.
“However, it is important to note that OXTR polymorphisms in the prairie vole robustly predict individual differences in OTR density in the NAc as well as pair bonding behavior (King et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites King et al., 2016 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThese experiments focused on OTRs in a single SSN nucleus in male prairie voles.
“Thirdly, these experiments focused on OTRs in a single SSN nucleus in male prairie voles. Future investigations of other steroid and neuropeptide systems, additional brain areas, female subjects, and alternative behavioral contexts and species are needed.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataSociosexual interaction and mating, but not OTR blockade in the NAc, strongly influenced levels of Fos-ir across SSN nuclei.
“These results suggest that sociosexual interaction and mating, but not OTR blockade in the NAc, strongly influenced levels of Fos-ir across SSN nuclei.”
- Also stated in: § 3.3. Fos-ir across the SSN · boosted
“interaction and mating, but not OTR blockade in the NAc, strongly influenced levels of Fos-ir across SSN nuclei.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The SSN is a neural network that modulates selective social attachment and other forms of associative social learning by attaching valence and incentive salience to sociosensory cues.
- Also stated in: § 3.3. Fos-ir across the SSN · boosted
Classified as probably not a substantial claim.
Study design and conductreasoningBatch was included as a random effect in all linear mixed-effects regression analyses of raw Fos-ir count values to control for differences between batches.
“To control for differences between batches, batch was included as a random effect in all linear mixed-effects regression analyses of raw Fos-ir count values.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims. The quote only partly states this claim.
Study design and conductown dataAnatomical placement of cannula implants was validated and subjects were included only if the cannulation track terminated within 0.5 mm of the dorsal NAc.
“Subjects were included if the cannulation track terminated within 0.5 mm of the dorsal NAc.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningCentral and region-specific OTR signaling contribute to individual and species diversity in distributed neural network function during social contexts.
“Taken together, these experiments are consistent with hypotheses that central and region-specific OTR signaling contribute to individual and species diversity in distributed neural network function during social contexts.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningOTR-mediated promotion of transient network states improves transmission from other nodes of the SSN to the NAc shell, facilitating attachment of salience and valence to sociosensory cues and thereby promoting social learning.
“This may occur in part through OTR-mediated promotion of transient network states that improve transmission from other nodes of the SSN to the NAc shell, facilitating attachment of salience and valence to sociosensory cues and thereby promoting social learning.”
Quote in the paperSubstantial claim- Rests on an assumption: Correlated Fos-ir between brain regions reflects functional coupling between neuronal populations.
Classified as probably not a substantial claim.
Study design and conductreasoningAnalyses of Fos-ir were restricted to subjects that mated during cohabitation to maximize divergence in presumed OT signaling between socially-exposed treatment groups.
“analyses of Fos-ir were restricted to subjects that mated during cohabitation (aCSF, n = 11; OTA, n = 12) to maximize divergence in presumed OT signaling (mating induces OT release) between socially-exposed treatment groups”
Quote in the paperSubstantial claim- Rests on an assumption: Mating induces OT release.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataOne subject (aCSF-treated, unexposed) was excluded due to significant backflow during infusion.
“One subject (aCSF-treated, unexposed) was excluded due to significant backflow during infusion”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataTwo subjects were excluded; one (OTA-treated, exposed) due to an anterior miss, and a second (aCSF-treated, exposed) due to extensive unilateral leakage of blood through the cannula and into the NAc.
“Two subjects were excluded; one (OTA-treated, exposed) due to an anterior miss, and a second (aCSF-treated, exposed) due to extensive unilateral leakage of blood through the cannula and into the NAc.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMethylation of OXTR in peripheral blood cells is associated with decreased correlated fluctuations in BOLD responses among limbic and cortical regions while viewing fearful and angry faces.
“Two studies have shown that naturally-occurring polymorphisms in human OXTR (the gene encoding OTR) are associated with correlated fluctuations in BOLD responses between hypothalamic, limbic, and/or cortical brain areas during social tasks (Tost et al., 2010; Tost et al., 2011), and one has shown that methylation of OXTR in peripheral blood cells is associated with decreased correlated fluct”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Puglia et al., 2015 source
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable).
Interpretationown dataThese data advance our understanding of how neuropeptide systems modulate distributed network function.
“Despite these limitations, these data advance our understanding of how neuropeptide systems modulate distributed network function.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe hypothesis that central OTR activation modulates correlated activity across distributed brain networks is consistent with continually emerging data from experiments in primates.
“The hypothesis that central OTR activation modulates correlated activity across distributed brain networks is consistent with continually emerging data from experiments in primates.”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenNeuronal phenotypes and anatomical projections of Fos-positive neurons within each SSN nucleus are unknown, limiting identification of anatomically interconnected neuronal subpopulations that become functionally connected during social contexts.
“Firstly, the neuronal phenotypes and anatomical projections of Fos-positive neurons within each SSN nucleus are unknown, and therefore identifying anatomically interconnected neuronal subpopulations that become functionally connected during social contexts is a critical area for future investigation.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNaturally-occurring polymorphisms in human OXTR are associated with correlated fluctuations in BOLD responses between hypothalamic, limbic, and/or cortical brain areas during social tasks.
“Two studies have shown that naturally-occurring polymorphisms in human OXTR (the gene encoding OTR) are associated with correlated fluctuations in BOLD responses between hypothalamic, limbic, and/or cortical brain areas during social tasks (Tost et al., 2010; Tost et al., 2011), and one has shown that methylation of OXTR in peripheral blood cells is associated with decreased correlated fluct”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim. May combine two claims.
PremisecitationCentral Fos-ir reflects rapid adaptation of neuronal and synaptic physiology in response to synaptic input through robust transcriptional regulation, and has been linked with depolarization in many, but not all, neuronal phenotypes.
“Thus, central Fos-ir is thought to reflect rapid adaptation of neuronal and synaptic physiology in response to synaptic input through robust transcriptional regulation, and has been linked with depolarization in many, but not all, neuronal phenotypes.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Kawashima et al., 2014 source
Not checked in the free run.
- cites Lyons and West, 2011
Not checked in the free run.
The paper relies on this without support.
Few studies have directly tested links between neuropeptide signaling and distributed network function.
“Although hypothesized links between neuropeptide signaling and distributed network function are consistent with a large body of literature, few studies have directly tested them.”
The paper relies on this without support.
No experiments to date have tested whether endogenous activation of region-specific OTR populations during social contexts modulates activity-dependent markers across distributed neural networks.
“To our knowledge, no experiments to date have tested whether endogenous activation of region-specific OTR populations during social contexts modulates activity-dependent markers (e.g. IEGs) across distributed neural networks.”
The paper relies on this without support.
Mating induces OT release.
“mating induces OT release”
The authors state this as an assumption.
The SSN is a neural network that modulates selective social attachment and other forms of associative social learning by attaching valence and incentive salience to sociosensory cues.
“Briefly, the SSN is a neural network that is hypothesized to modulate selective social attachment and other forms of associative social learning by attaching valence and incentive salience to sociosensory cues.”
The paper relies on this without support.
OTA selectively blocks OTRs in the NAc without affecting other receptors or brain regions.
“Because we used a selective OTR antagonist to manipulate OTR signaling specifically within the NAc, we tested whether this manipulation influenced local Fos-ir.”
The paper relies on this without support.
Correlated Fos-ir between brain regions reflects functional coupling between neuronal populations.
“Given the anatomical connectivity between the NAc shell and other SSN nuclei, these data raise the possibility that activation of accumbal OTRs during sociosexual interaction and mating modulates functional coupling between neuronal populations embedded within the NAc shell and neuronal populations embedded across SSN nuclei.”
The paper relies on this without support.
The NAc shell and other SSN nuclei are anatomically connected.
“Given the anatomical connectivity between the NAc shell and other SSN nuclei, these data raise the possibility that activation of accumbal OTRs during sociosexual interaction and mating modulates functional coupling between neuronal populations embedded within the NAc shell and neuronal populations embedded across SSN nuclei.”
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?
In prairie voles, OT signaling stimulated by mating enhances the coordinated activity of multiple brain regions in a social salience network, with OXTR signaling in the NAc acting as a hub for coordinating activity among AON, PVN, BLA, and PFC.
“In prairie voles, OT signaling stimulated by mating enhances the coordinated activity of multiple brain regions in a social salience network, a grouping of interconnected nodes thought to encode the valence and incentive salience of socio-sensory cues. OXTR signaling in the NAc acts as a hub for coordinating activity among AON, PVN, BLA, and PFC [124].”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [124]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredOxytocin, released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone.
“Oxytocin1,2,9–15, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone.”
From Oxytocin neurons enable social transmission of maternal behaviour (2021) · cites this paper as [11]
In sensory pathways, oxytocin signaling increases the salience of social stimuli by modulating neuron excitability and facilitates the flow of social information across the brain.
“In sensory pathways, oxytocin signaling increases the salience of social stimuli by modulating neuron excitability and facilitates the flow of social information across the brain [15].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [15]
OXT action results in modulation of neuronal activity in brain areas regulating social behaviors to increase the salience and reinforcing value of social stimuli.
“OXT action results in modulation of neuronal activity in brain areas regulating social behaviors 17 to increase the salience and reinforcing value of social stimuli 18,19.”
From Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles (2022) · cites this paper as [17]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Behavior ANOVA reports one numerator degree of freedom for five behaviors
MinorThe analysis treats five behaviors as a within-subject factor, so its uncorrected main effect and treatment-by-behavior interaction have 5 − 1 = 4 numerator degrees of freedom, not 1 as reported.
Reported 1 · recomputed 4
“a two-way repeated-measures ANOVA revealed a significant main effect of behavior (non-interaction, investigation, mounting, intromission, or huddling; F1,109 = 68.00; p < 0.001”
Residual-variance F-test has incompatible degrees of freedom
MinorThe mated groups contain 12 OTA-treated and 11 aCSF-treated animals. An F-test comparing their sample variances would have numerator and denominator degrees of freedom based on those group sizes minus one, not 1 and 20.
Reported 1 · recomputed 11
“the variance of MLR residuals was significantly greater in OTA- (σ2 = 0.82) compared to aCSF- (σ2 = 0.05) treated subjects (F-test; F1,20 = 17.25, p < 0.001; Fig. 2B).”
The citation lists haven’t been fetched yet
References 82 · Cited by 113
- Authors
- Johnson, Z. V., Walum, H., Xiao, Y., Riefkohl, P. C., & Young, L. J.
- Affiliations
- Emory University (US)
- Corresponding author
- Johnson, Zachary V.
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 87
- Pages
- 16-24
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC5207344
- OpenAlex
- W2546187937
- Semantic Scholar
- c0152eb2d2b5d5dbd49dc98f11668d5c61c3a2e3
- Cited by
- 113
- References
- 82
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 4 · 2023: 11 · 2022: 9 · 2021: 16 · 2020: 24 · 2019: 9 · 2018: 13 · 2017: 7 · 2016: 1
- FWCI
- 15.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01MH096983, 1P50MH100023)
- NIH Office of Research Infrastructure Programs (OD P51OD11132)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- oxytocin receptor, nucleus accumbens, Microtus ochrogaster, oxytocin receptor antagonist, Fos expression, mating behavior, social attachment, incentive salience, social behavior, neuropeptide signaling
- MeSH terms
- Animals, Behavior, Animal, Brain, Arvicolinae, Female, Male, Nerve Net, Nucleus Accumbens, Oxytocin, Pair Bond, Reproduction, Sexual Behavior, Animal, Social Behavior, Receptors, Oxytocin
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