Oxytocin receptors are widely distributed in the prairie vole (Microtus ochrogaster) brain: Relation to social behavior, genetic polymorphisms, and the dopamine system

May combine two claims.

Protein and mRNA expression were closely aligned in most brain regions, but not all.

“Protein and mRNA expression were closely aligned in most brain regions, but not all.”

May combine two claims.

Oxtr mRNA expression is widespread and diffuse throughout the prairie vole brain, with specific areas displaying particularly robust expression.

“We found that oxytocin receptor mRNA expression was widespread and diffuse throughout the brain, with specific areas displaying particularly robust expression.”

• Also stated in: § Brain-wide mapping of Oxtr mRNA · plain

  “Diffuse expression of Oxtr can be seen in numerous regions throughout the brain, with robust expression concentrated in specific regions.”

May combine two claims.

Weak genotype-by-sex and genotype-by-cell type interactions were detected, accounting for 4.21% and 0.50% of variation, respectively.

“Weak genotype-by-sex (F (1, 20) = 4.41, p = 0.0485) and genotype-by-cell type (F (1, 30) = 4.80, p = 0.0405) interactions were also detected, accounting for 4.21% and 0.50% of variation, respectively, in which genotype had slightly larger effects on females than on males and on D2R cells than on D1R cells.”

May combine two claims.

Oxtr mRNA expression in cerebral cortex was relatively diffuse, with certain regions containing moderate-to-high levels, primarily in cortical layers 2, 5, and 6.

“Oxtr mRNA expression in cerebral cortex was relatively diffuse, with certain regions containing moderate-to-high levels of expression (Figure 1). These signals were primarily located in cortical layers 2, 5, and 6 (Figure 4).”

May combine two claims.

The BNST, VMH, and paraventricular thalamic nucleus displayed exceptionally strong Oxtr expression, while the medial preoptic area and lateral septum contained more moderate levels.

“The BNST, VMH, and paraventricular thalamic nucleus displayed exceptionally strong expression, while the medial preoptic area and lateral septum contained more moderate levels of Oxtr mRNA.”

May combine two claims.

All regions of the PFC including prelimbic and infralimbic cortex contained Oxtr mRNA, with strong expression more prominent in deeper cortical layers 5 and 6 in the prelimbic cortex.

“Both the core and shell of the NAc, a critical reward center, contained high levels of Oxtr mRNA (Figure 2d), as did all regions of the PFC including prelimbic and infralimbic cortex, although strong expression was more prominent in deeper cortical layers, particularly 5 and 6, in the prelimbic cortex (Figure 1,2c).”

May combine two claims.

Oxtr mRNA-producing cells were identified in certain hypothalamic areas and related structures including the VMH, lateral septum, medial preoptic area, paraventricular thalamus, paraventricular nucleus of the hypothalamus, and BNST, with more intense signal in the lateral division.

“Oxtr mRNA-producing cells were identified in certain hypothalamic areas and related structures involved in social and reproductive behavior including the VMH (Figure 3f), lateral septum (Figure 3a), medial preoptic area (Figure 3c), paraventricular thalamus (Figure 3d), paraventricular nucleus of the hypothalamus (Figure 3e), and BNST, with more intense signal in the lateral division (Figure 3b).”

May combine two claims.

Oxtr mRNA was detected throughout the amygdala, with particularly dense expression in the central and basolateral regions and the posteromedial cortical amygdala.

“Oxtr mRNA was detected throughout the amygdala, which processes olfactory information and modulates valence, and expression was particularly dense in the central and basolateral regions (Figure 2e) and the posteromedial cortical amygdala (Figure 1).”

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

There was a main effect of cell type on Oxtr expression, with slightly more Oxtr signal in D2R cells than D1R cells, accounting for 2.18% of variation.

“although slightly more Oxtr signal was detected in D2R cells than in D1R cells, cell type accounted for just 2.18% of variation.”

May combine two claims.

Both OXTR protein and Oxtr mRNA were strongly expressed in stratum pyramidale of hippocampal CA2, but even stronger protein labeling in the absence of any mRNA signal was evident immediately superficial and deep to the stratum pyramidale.

“Both OXTR protein (Figure 6a,b) and Oxtr mRNA (Figure 6c,d) were strongly expressed in stratum pyramidale of hippocampal CA2, but even stronger protein labeling in the absence of any mRNA signal was evident immediately superficial and deep to the stratum pyramidale (Figure 6e,f).”

May combine two claims.

Oxtr mRNA is widely expressed across the prairie vole brain, with enrichment in particular brain regions.

“Our comprehensive analysis of Oxtr mRNA revealed widespread expression of Oxtr across the brain, with enrichment in particular brain regions, indicating that OXTR signaling may exert more profound modulation of brain function than expected from earlier receptor binding studies.”

• Also stated in: § Conclusion and future directions · plain

  “Our comprehensive, brain-wide analysis of Oxtr mRNA expression revealed diffuse, widespread distribution throughout the brain as well as robust expression restricted to specific brain regions.”

May combine two claims.

Oxtr mRNA was observed in many subregions of the hippocampus, with particularly strong expression in dorsal CA2 and ventral CA1.

“We observed Oxtr mRNA in many subregions of the hippocampus, but expression was particularly strong in dorsal CA2 and ventral CA1, regions studied extensively for their role in social memory.”

May combine two claims.

In prairie voles, extensive Oxtr labeling was observed in the amygdala, with particularly strong expression in the basolateral and central nuclei.

“In prairie voles, we observed extensive labeling in the amygdala, with particularly strong expression in the basolateral and central nuclei.”

May combine two claims.

Many cortical areas displayed sparse labeling of Oxtr mRNA, but some, including the anterior cingulate and insular cortices, showed strong labeling in restricted layers, primarily layers two, five, and six.

“Many cortical areas displayed sparse labeling of Oxtr mRNA, but some, including the anterior cingulate and insular cortices, showed strong labeling in restricted layers, primarily layers two, five, and six.”

May combine two claims.

High-Oxtr voles had considerable OXTR binding in the SNR, while Low-Oxtr voles showed no detectable binding there.

“We also observed that High-Oxtr voles had considerable OXTR binding in the SNR, while Low-Oxtr voles showed no detectable binding there.”

May combine two claims.

Oxtr was consistently expressed in the insular cortex and all the nodes of the SDMN.

“Oxtr was consistently expressed in the insular cortex and all the nodes of the SDMN.”

May combine two claims.

The CA2 region displayed strong expression of both Oxtr mRNA and OXTR protein.

“The CA2 region displayed strong expression of both Oxtr mRNA and OXTR protein.”

May combine two claims.

In CA2, Oxtr mRNA was restricted to the stratum pyramidale while OXTR protein labeling was evident both superficial and basal to the stratum pyramidale.

“The mRNA was restricted to the stratum pyramidale while protein labeling was evident both superficial and basal to the stratum pyramidale.”

May combine two claims.

There was no significant difference between D1R and D2R cells in Low-Oxtr males or in females of either genotype.

“There was also a significant difference between D1R and D2R cells in High-Oxtr males (p = 0.0053) with D2R cells expressing slightly more Oxtr, but there was no significant difference between D1R and D2R cells in Low-Oxtr males or in females of either genotype.”

May combine two claims.

Genotype had slightly larger effects on Oxtr expression in females than in males and in D2R cells than in D1R cells.

“in which genotype had slightly larger effects on females than on males and on D2R cells than on D1R cells.”

May combine two claims.

OXTRs can be transported to distal neuronal processes, consistent with presynaptic OXTR functions.

“indicating that oxytocin receptors can be transported to distal neuronal processes, consistent with presynaptic oxytocin receptor functions.”

• Also stated in: § Mismatch of Oxtr mRNA and OXTR protein · hedged

  “This disparity between the locations of OXTR protein and Oxtr mRNA suggests that OXTRs may be synthesized in the cell body in one location and transported to projections in another, enabling synaptic transmission.”

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

Autoradiography was performed on a small subset of sections from each brain to confirm that genotype predicted NAc OXTR density as expected.

“Autoradiography was performed on a small subset of sections from each brain to confirm that genotype predicted NAc OXTR density as expected.”

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

Our observations are consistent with previous studies labeling Oxtr mRNA in prairie voles.

“Our observations are consistent with previous studies labeling Oxtr mRNA in prairie voles, although these earlier efforts analyzed fewer anatomical regions and utilized in situ hybridization techniques that were far less sensitive and had lower resolution than those we employed in the present study (Lim, Murphy, & Young, 2004; L. J. Young et al., 1996).”

• cites Lim, Murphy, & Young, 2004Not checked yet

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• cites L. J. Young et al., 1996Not checked yet

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

Antibodies targeting OXTRs are notorious for producing non-specific labeling.

“Although Mitre et al.’s labeling in mice is convincing, antibodies targeting OXTRs are notorious for producing non-specific labeling (Yoshida et al., 2009).”

• cites Yoshida et al., 2009Not checked yet

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

Oxytocin is released in response to social stimuli including social touch, visual observation of maternal behavior, infant vocalizations, and interspecies eye contact between humans and dogs.

“Oxytocin is released in response to a myriad of social stimuli including social touch (Tang et al., 2020), visual observation of maternal behavior (Carcea et al., 2021), infant vocalizations (Valtcheva et al., 2021), and even interspecies eye contact between humans and dogs (Nagasawa et al., 2015).”

• cites Tang et al., 2020Not checked yet

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• cites Carcea et al., 2021Not checked yet

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• cites Valtcheva et al., 2021Not checked yet

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May combine two claims.

The high level of OXTR mRNA expression in human CPu and NAc is consistent with prairie vole, but not mouse or rat brain.

“Notably, the high level of OTXR mRNA expression in human CPu and NAc is consistent with prairie vole, but not mouse or rat brain.”

• cites Quintana et al., 2019Not checked yet

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Classified as probably not a substantial claim.

There has been no comprehensive mapping of Oxtr mRNA expression throughout the vole brain.

“Despite the value of the prairie vole model for understanding the effects of oxytocin on behavior, there has been no comprehensive mapping of Oxtr mRNA expression throughout the vole brain.”

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

Species- and brain region-specific developmental changes in OXTR density have been reported in rodents.

“It should be noted that species- and brain region-specific developmental changes in OXTR density have been reported in rodents, which our study cannot address since only adult animals were used.”

• cites Prounis, Thomas, & Ophir, 2018Not checked yet

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• cites Smith et al., 2016Not checked yet

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Classified as probably not a substantial claim.

Previous OXTR localization studies in voles relied on autoradiographic detection, which does not provide cellular resolution.

“Previous OXTR localization studies in voles have relied on autoradiographic detection, which does not provide cellular resolution.”

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

Mice show intermediate to high levels of OXTR immunolabeling in the PVN, SON, and SCN.

“Intermediate to high level of OXTR immunolabeling was detected in the mouse PVN, SON and SCN, whereas only small population of cells expressed Oxtr mRNA in these nuclei of the prairie vole.”

• cites Mitre et al., 2016Not checked yet

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May combine two claims.

In prairie voles, SNPs in the OXTR gene Oxtr predict individual differences in OXTR density in the NAc, but not other areas, which, in turn, predicts social attachment behaviors and resilience to early-life neglect.

“In prairie voles, single nucleotide polymorphisms (SNPs) in the OXTR gene, Oxtr, predict individual differences in OXTR density in the NAc, but not other areas, which, in turn, predicts social attachment behaviors and resilience to early-life neglect (Ahern, Olsen, Tudino, & Beery, 2021; Barrett, Arambula, & Young, 2015; King, Walum, Inoue, Eyrich, & Young, 2016).”

• cites Ahern, Olsen, Tudino, & Beery, 2021Not checked yet

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• cites Barrett, Arambula, & Young, 2015Not checked yet

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• cites King, Walum, Inoue, Eyrich, & Young, 2016Not checked yet

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

Once released, oxytocin can modulate neural network activity by directly depolarizing projection neurons, affecting interneurons that regulate local circuit activity, and modulating other neuromodulator systems like dopamine, acetylcholine, and serotonin.

“Once released, oxytocin is capable of modulating the activity of neural networks at three levels: i) by directly depolarizing projection neurons, ii) by affecting the activity of interneurons that regulate local circuit activity, and iii) by modulating the activity of other neuromodulator systems like dopamine, acetylcholine, and serotonin (Froemke & Young, 2021; Putnam, Young, & Gothard, 2018).”

• cites Froemke & Young, 2021Not checked yet

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• cites Putnam, Young, & Gothard, 2018Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

Our study cannot address developmental changes in Oxtr mRNA because only adult animals were used.

“It should be noted that species- and brain region-specific developmental changes in OXTR density have been reported in rodents, which our study cannot address since only adult animals were used.”

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

In prairie voles, OXTR binding increases from juvenile to adulthood in the NAc, CPu, BLA, and PVA, whereas in rats OXTR binding significantly decreases in several of the same regions as they mature.

“For instance, in the NAc, CPu, BLA and PVA, OXTR binding increases from juvenile to the adulthood in prairie voles, whereas OXTR binding is significantly decreased in several of the same regions as rats mature into adults (Prounis, Thomas, & Ophir, 2018; Smith et al., 2016).”

• cites Prounis, Thomas, & Ophir, 2018Not checked yet

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• cites Smith et al., 2016Not checked yet

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

Only the male High-Oxtr brain was used to generate Supplementary Table 1, though this expression pattern was consistent across the other three brains except for lower expression in genotype-dependent regions such as NAc and CPu of Low-Oxtr voles.

“Only the male High-Oxtr brain was used to generate Supplementary Table 1, though this expression pattern was consistent across the other three brains except for the lower expression in genotype-dependent regions such as NAc and CPu of Low-Oxtr voles.”

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

In humans, Oxtr mRNA expression is widespread and diffuse with isolated regions of high expression including the striatum, thalamus, hypothalamus, hippocampus, amygdala, and olfactory bulbs.

“In humans, Oxtr mRNA expression appears similarly widespread and diffuse with isolated regions of high expression including the striatum, thalamus, hypothalamus, hippocampus, amygdala, and olfactory bulbs (Bethlehem et al., 2017; Quintana et al., 2019).”

• cites Bethlehem et al., 2017Not checked yet

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• cites Quintana et al., 2019Not checked yet

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

Our findings are generally consistent with protein and mRNA analyses of Oxtr expression patterns in other species.

“Although species differences exist, our findings are generally consistent with protein and mRNA analyses of Oxtr expression patterns in other species.”

• AssumptionRests on an assumption: Findings from other species about OXTR function in homologous brain regions generalize to prairie voles.

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

Multi-sensory social information is processed in dorsal CA2, then transmitted to ventral CA1 for social memory storage.

“Multi-sensory social information is believed to be processed in dorsal CA2, then transmitted to ventral CA1 for social memory storage (Watarai, Tao, Wang, & Okuyama, 2021).”

• cites Watarai, Tao, Wang, & Okuyama, 2021Not checked yet

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May combine two claims.

Oxytocin-dependent salience of olfactory social cues is enhanced during mating, which facilitates pair bonding.

“OXTR binding in the prairie vole anterior olfactory area is highly sensitive to estrogen, suggesting that oxytocin-dependent salience of olfactory social cues is enhanced during mating, which facilitates pair bonding (Witt, Carter, & Lnsel, 1991).”

• cites Witt, Carter, & Lnsel, 1991Not checked yet

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May combine two claims.

Oxytocin signaling in the BNST and NAc mediates social vigilance and the regulation of social approach behaviors.

“Oxytocin signaling in the BNST and NAc mediates social vigilance and the regulation of social approach behaviors (Duque-Wilckens et al., 2020; Williams et al., 2020).”

• cites Duque-Wilckens et al., 2020Not checked yet

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• cites Williams et al., 2020Not checked yet

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

OXTR signaling in the anterior olfactory area enhances social recognition in mice by increasing excitatory output to inhibitory granule cell interneurons in the main olfactory bulb.

“OXTR signaling in the anterior olfactory area enhances social recognition in mice by increasing excitatory output to inhibitory granule cell interneurons in the main olfactory bulb (Oettl et al., 2016).”

• cites Oettl et al., 2016Not checked yet

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May combine two claims.

Prairie voles have high densities of OXTR binding in the basolateral amygdala, whereas mice do not.

“Interestingly, while prairie voles have high densities of OXTR binding in the basolateral amygdala, mice do not (Larry J. Young & Zhang, 2021).”

• cites Larry J. Young & Zhang, 2021Not checked yet

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May combine two claims.

In mice, OXTR binding depolarizes CA2 pyramidal cells, regulating short-term plasticity of CA2-to-CA1 synaptic transmission.

“Indeed, dorsal CA2 provides strong excitatory input to ventral CA1 (Meira et al., 2018) and in mice, OXTR binding depolarizes CA2 pyramidal cells, which regulates the short-term plasticity of CA2-to-CA1 synaptic transmission (Tirko et al., 2018).”

• cites Tirko et al., 2018Not checked yet

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May combine two claims.

Oxytocin signaling might be involved in the information processing of the accessory olfactory system and the influence of this system on sociosexual behavior.

“Thus, oxytocin signaling might be involved in the information processing of the accessory olfactory system and the influence of this system on sociosexual behavior.”

• AssumptionRests on an assumption: The posteromedial cortical amygdaloid nucleus is the only cortical target of the direct projection from the accessory olfactory bulb.

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

Oxytocin signaling in the medial amygdala is essential for social recognition in mice.

“Oxytocin signaling in the medial amygdala is also essential for social recognition in mice (Ferguson, Aldag, Insel, & Young, 2001), and in the central amygdala, oxytocin signaling modulates emotion discrimination (Ferretti et al., 2019).”

• cites Ferguson, Aldag, Insel, & Young, 2001Not checked yet

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

This increased inhibition enhances the signal-to-noise ratio of social olfactory information conveyed via mitral and tufted cell projection neurons from the olfactory bulb to olfactory cortex.

“This increased inhibition enhances the signal-to-noise ratio of social olfactory information conveyed via mitral and tufted cell projection neurons from the olfactory bulb to olfactory cortex (Oettl et al., 2016).”

• cites Oettl et al., 2016Not checked yet

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

Ventral CA1 houses social engrams, or memory traces for specific individuals.

“Ventral CA1 is believed to house social engrams, or memory traces for specific individuals (Okuyama, 2018; Okuyama, Kitamura, Roy, Itohara, & Tonegawa, 2016), and oxytocin signaling in CA1 fast-spiking interneurons enhances signal-to-noise ratio in CA1 pyramidal cells (Owen et al., 2013).”

• cites Okuyama, 2018Not checked yet

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• cites Okuyama, Kitamura, Roy, Itohara, & Tonegawa, 2016Not checked yet

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May combine two claims.

OXTRs in CA2 are necessary for discrimination of social stimuli and formation of social recognition memory.

“Dorsal CA2 and its projections to ventral CA1 are critical for social memory encoding, consolidation, and recall (Meira et al., 2018; Oliva, Fernández-Ruiz, Leroy, & Siegelbaum, 2020), and OXTRs in CA2 are necessary for discrimination of social stimuli and formation of social recognition memory (Lin et al., 2018; Raam, McAvoy, Besnard, Veenema, & Sahay, 2017).”

• cites Lin et al., 2018Not checked yet

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• cites Raam, McAvoy, Besnard, Veenema, & Sahay, 2017Not checked yet

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

Oxytocin signaling in CA1 fast-spiking interneurons enhances signal-to-noise ratio in CA1 pyramidal cells.

“Ventral CA1 is believed to house social engrams, or memory traces for specific individuals (Okuyama, 2018; Okuyama, Kitamura, Roy, Itohara, & Tonegawa, 2016), and oxytocin signaling in CA1 fast-spiking interneurons enhances signal-to-noise ratio in CA1 pyramidal cells (Owen et al., 2013).”

• cites Owen et al., 2013Not checked yet

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May combine two claims.

OXTR binding in hippocampal subfields, particularly dorsal CA2 and ventral CA1, appears to modulate hippocampal network activity and facilitate the flow of social information through the hippocampus, enabling social discrimination and memory.

“OXTR binding in hippocampal subfields, particularly dorsal CA2 and ventral CA1, therefore appears to modulate hippocampal network activity and facilitate the flow of social information through the hippocampus, thus enabling social discrimination and memory.”

May combine two claims.

OXTR signaling in the NAc of virgins decreases the amplitude of spontaneous EPSCs, while it increases the amplitude of electrically evoked EPSCs in an endocannabinoid-dependent manner in the NAc of pair-bonded voles.

“OXTR signaling in the NAc of virgins decreases the amplitude of spontaneous excitatory postsynaptic currents (EPSCs), while it increases the amplitude of electrically evoked EPSCs in an endocannabinoid-dependent manner in the NAc of pair-bonded voles (Borie et al., 2022).”

• cites Borie et al., 2022Not checked yet

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

In the central amygdala, oxytocin signaling modulates emotion discrimination.

“Oxytocin signaling in the medial amygdala is also essential for social recognition in mice (Ferguson, Aldag, Insel, & Young, 2001), and in the central amygdala, oxytocin signaling modulates emotion discrimination (Ferretti et al., 2019).”

• cites Ferretti et al., 2019Not checked yet

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

Somatodendritic release of oxytocin in the paraventricular and supraoptic nuclei is believed to have local autocrine and paracrine effects with important behavioral consequences.

“For example, somatodendritic release of oxytocin in the paraventricular and supraoptic nuclei is believed to have local autocrine and paracrine effects with important behavioral consequences (Mike Ludwig, Apps, Menzies, Patel, & Rice, 2016; M. Ludwig & Leng, 2006; Modi et al., 2015).”

• cites Mike Ludwig, Apps, Menzies, Patel, & Rice, 2016Not checked yet

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• cites M. Ludwig & Leng, 2006Not checked yet

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• cites Modi et al., 2015Not checked yet

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

The anatomical origins and physiological regulation of oxytocin release in the central nervous system are complicated and not fully understood, but rely on parvocellular projections, magnocellular axon collaterals, and extra-synaptic oxytocin release.

“The anatomical origins and physiological regulation of oxytocin release in the central nervous system are more complicated and not fully understood, but certainly rely on parvocellular projections, magnocellular axon collaterals, and extra-synaptic oxytocin release (Althammer & Grinevich, 2017; Grinevich & Ludwig, 2021).”

• cites Althammer & Grinevich, 2017Not checked yet

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• cites Grinevich & Ludwig, 2021Not checked yet

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

Peripheral oxytocin signaling in the vagus nerve can influence feeding and drug self-administration behaviors.

“Notably, the vagus nerve nucleus showed strong labeling as well, as peripheral oxytocin signaling in the vagus nerve can influence feeding and drug self-administration behaviors (Everett, Turner, Costa, Baracz, & Cornish, 2021; Iwasaki et al., 2015), and therefore could potentially mediate some of the behavioral effects of intranasally administered oxytocin in humans.”

• cites Everett, Turner, Costa, Baracz, & Cornish, 2021Not checked yet

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• cites Iwasaki et al., 2015Not checked yet

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

Peripheral oxytocin signaling could potentially mediate some of the behavioral effects of intranasally administered oxytocin in humans.

“Notably, the vagus nerve nucleus showed strong labeling as well, as peripheral oxytocin signaling in the vagus nerve can influence feeding and drug self-administration behaviors (Everett, Turner, Costa, Baracz, & Cornish, 2021; Iwasaki et al., 2015), and therefore could potentially mediate some of the behavioral effects of intranasally administered oxytocin in humans.”

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

A small population of parvocellular neurons in the paraventricular nucleus is selectively activated by social touch, and these cells project to and regulate the activity of magnocellular neurons.

“Additionally, a recent study found that a small population of parvocellular neurons in the paraventricular nucleus is selectively activated by social touch, and that these cells project to and regulate the activity of magnocellular neurons (Tang et al., 2020).”

• cites Tang et al., 2020Not checked yet

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

Oxtr mRNA in the mouse PAG showed decline from juvenile to adulthood.

“Oxtr mRNA in the mouse PAG also showed decline from juvenile to adulthood (Daniel E. Olazábal & Alsina-Llanes, 2016).”

• cites Daniel E. Olazábal & Alsina-Llanes, 2016Not checked yet

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

Oxtr expression in the rat VTA was decreased during development and only weak expression was detected in the adult.

“Consistent with our sparse Oxtr labeling in the adult prairie vole VTA, Oxtr expression in the rat VTA was decreased during development and only weak expression was detected in the adult (Yoshimura, Kimura, Watanabe, & Kiyama, 1996).”

• cites Yoshimura, Kimura, Watanabe, & Kiyama, 1996Not checked yet

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

Via their projections into the posterior pituitary, magnocellular neurons are the primary source of oxytocin released as a hormone into peripheral circulation.

“Via their projections into the posterior pituitary, magnocellular neurons are the primary source of oxytocin released as a hormone into peripheral circulation.”

• cites Althammer & Grinevich, 2017Not checked yet

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• cites Grinevich & Ludwig, 2021Not checked yet

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

Oxytocin is synthesized and released primarily by the magnocellular and parvocellular neurons of the paraventricular and supraoptic nuclei as well as accessory nuclei.

“Oxytocin is synthesized and released primarily by the magnocellular and parvocellular neurons of the paraventricular and supraoptic nuclei as well as accessory nuclei (Althammer & Grinevich, 2017; Grinevich & Ludwig, 2021).”

• cites Althammer & Grinevich, 2017Not checked yet

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• cites Grinevich & Ludwig, 2021Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Despite the small proportion of neurons expressing Oxtr, they may be sufficient to trigger functional effects through collateral activation of interconnected magnocellular neurons.

“Despite the small proportion of neurons expressing Oxtr, they may be sufficient to trigger functional effects through collateral activation of interconnected magnocellular neurons.”

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

Rats have robust Oxtr expression in the ventrolateral portion of the VMH, and this expression influences sexual behavior and is regulated by estrogen and progesterone.

“In contrast, rats have robust Oxtr expression in the ventrolateral portion of the VMH, and this expression influences sexual behavior and is regulated by estrogen and progesterone (Bale, Dorsa, & Johnston, 1995; Schumacher, Coirini, Pfaff, & McEwen, 1990).”

• cites Bale, Dorsa, & Johnston, 1995Not checked yet

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• cites Schumacher, Coirini, Pfaff, & McEwen, 1990Not checked yet

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

The origin of the OXTR protein signal observed cannot be determined definitively from our images.

“Although the origin of the OXTR protein signal we observed cannot be determined definitively from our images, it is clear that the proteins reside and act in receptive fields a considerable distance from the somas in which the mRNA resides.”

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

The canonical notion of D1R and D2R MSNs is that they project to the SNR either directly via the monosynaptic direct pathway or indirectly via the multi-synaptic indirect pathway, respectively.

“Although oversimplified, the canonical notion of D1R and D2R MSNs is that they project to the SNR either directly via the monosynaptic “direct pathway” or indirectly via the multi-synaptic “indirect pathway,” respectively (Calabresi, Picconi, Tozzi, Ghiglieri, & Di Filippo, 2014).”

• cites Calabresi, Picconi, Tozzi, Ghiglieri, & Di Filippo, 2014Not checked yet

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

The OXTR protein labeling observed superficial and basal to the stratum pyramidale is plausibly located on the dendritic arbors of pyramidal neurons.

“It is therefore plausible that the OXTR protein labeling we observed superficial and basal to the stratum pyramidale is located on the dendritic arbors of pyramidal neurons.”

May combine two claims.

In mice, CA2 receives afferent projections from the paraventricular nucleus of the hypothalamus, and CA2 pyramidal cells express robust levels of OXTRs, which maintain long-term potentiation of synapses with entorhinal cortex projections.

“Nevertheless, in mice, CA2 receives afferent projections from the paraventricular nucleus of the hypothalamus, and CA2 pyramidal cells express robust levels of OXTRs, which maintain the long-term potentiation of synapses with entorhinal cortex projections (Cui, Gerfen, & Young, 2013; Lin et al., 2018; Yoshida et al., 2009).”

• cites Cui, Gerfen, & Young, 2013Not checked yet

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• cites Lin et al., 2018Not checked yet

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• cites Yoshida et al., 2009Not checked yet

  Not checked in the free run.

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

In humans, the dorsal anterior cingulate cortex and anterior insular cortex constitute key nodes of a salience network critical for detection of behaviorally relevant stimuli and commonly disrupted in neuropsychiatric conditions.

“Notably, in humans, the dorsal anterior cingulate cortex and anterior insular cortex constitute the key nodes of a salience network, which is critical for the detection of behaviorally relevant stimuli and commonly disrupted in neuropsychiatric conditions (Seeley et al., 2007; Uddin, 2015).”

• cites Seeley et al., 2007Not checked yet

  Not checked in the free run.

• cites Uddin, 2015Not checked yet

  Not checked in the free run.

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

The genotype-dependent OXTR binding observed in the ventral pallidum of High-Oxtr voles is from OXTR proteins on terminals of axons from NAc.

“Like the SNR, the ventral pallidum receives strong direct projections from the NAc, and we suspect that the genotype-dependent OXTR binding we observed in the ventral pallidum of High-Oxtr voles is from OXTR proteins on the terminals of axons from NAc.”

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

Both D1R and D2R MSNs receive afferent input from a wide range of brain regions.

“Both D1R and D2R MSNs receive afferent input from a wide range of brain regions (Z. Li et al., 2018).”

• cites Z. Li et al., 2018Not checked yet

  Not checked in the free run.

May combine two claims.

In prairie voles, D2R activation facilitates pair bond formation, and either blocking D2Rs or activating D1Rs inhibits pair bond formation.

“In prairie voles, D2R activation facilitates pair bond formation, and either blocking D2Rs or activating D1Rs inhibits pair bond formation (Aragona et al., 2006).”

• cites Aragona et al., 2006Not checked yet

  Not checked in the free run.

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

The primary projection neurons of the NAc, GABAergic MSNs, constitute approximately 95% of all neurons in the NAc and can be subdivided into those that express Drd1 and those that express Drd2.

“The primary projection neurons of the NAc, GABAergic MSNs, constitute approximately 95% of all neurons in the NAc and can be subdivided into those that express Drd1 and those that express Drd2.”

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

The anterior cingulate and insular cortices share reciprocal connectivity, suggesting a mechanism by which OXTRs in these regions could coordinate activity between two distinct cortical areas and thus regulate emotion detection and behavioral responses.

“The anterior cingulate and insular cortices share reciprocal connectivity, suggesting a mechanism by which OXTRs in these regions could coordinate activity between two distinct cortical areas and thus regulate emotion detection and behavioral responses.”

May combine two claims.

A set of SNPs in linkage disequilibrium in the prairie vole Oxtr gene predicts both the animal's ability to form a pair bond and the density of OXTR protein expressed in the NAc, CPu, OB, and anterior olfactory area.

“We previously identified a set of SNPs in linkage disequilibrium in the prairie vole Oxtr gene that predicts both the animal’s ability to form a pair bond and the density of OXTR protein expressed in the NAc, CPu, OB, and anterior olfactory area (King et al., 2016).”

• cites King et al., 2016Not checked yet

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

OXTR binding patterns have been shown to vary widely between rodent species.

“It is important to note that OXTR binding patterns have been shown to vary widely between rodent species (Raggenbass, Tribollet, Dubois-Dauphin, & Dreifuss, 1989; Larry J. Young & Zhang, 2021).”

• cites Raggenbass, Tribollet, Dubois-Dauphin, & Dreifuss, 1989Not checked yet

  Not checked in the free run.

• cites Larry J. Young & Zhang, 2021Not checked yet

  Not checked in the free run.

May combine two claims.

OXTRs may act in receptive fields after being transported a considerable distance from somas containing Oxtr mRNA, consistent with both pre- and post-synaptic signaling mechanisms.

“Furthermore, our comparison of Oxtr mRNA and OXTR protein localization in adjacent slices suggests that OXTRs may act in receptive fields after being transported a considerable distance from somas containing Oxtr mRNA, consistent with both pre- and post-synaptic signaling mechanisms.”