Insular cortex projections to nucleus accumbens core mediate social approach to stressed juvenile rats
Open accessPublished version of a preprint
Abstract
Social interactions are shaped by features of the interactants, including age, emotion, sex, and familiarity. Age-specific responses to social affect are evident when an adult male rat is presented with a pair of unfamiliar male conspecifics, one of which is stressed via two foot shocks and the other naive to treatment. Adult test rats prefer to interact with stressed juvenile (postnatal day 30, PN30) conspecifics but avoid stressed adult (PN50) conspecifics. This pattern depends upon the insular cortex (IC), which is anatomically connected to the nucleus accumbens core (NAc). The goal of this work was to test the necessity of IC projections to NAc during social affective behavior. Here, bilateral pharmacological inhibition of the NAc with tetrodotoxin (1 μ m ; 0.5 μl/side) abolished the preference for stressed PN30, but did not alter interactions with PN50 conspecifics. Using a combination of retrograding tracing and c-Fos immunohistochemistry, we report that social interactions with stressed PN30 conspecifics elicit greater Fos immunoreactivity in IC → NAc neurons than interactions with naive PN30 conspecifics. Chemogenetic stimulation of IC terminals in the NAc increased social exploration with juvenile, but not adult, conspecifics, whereas chemogenetic inhibition of this tract blocked the preference to investigate stressed PN30 conspecifics, which expands upon our previous finding that optogenetic inhibition of IC projection neurons mediated approach and avoidance. These new findings suggest that outputs of IC to the NAc modulate social approach, which provides new insight to the neural circuitry underlying social decision-making. SIGNIFICANCE STATEMENT Social decision-making underlies an animal's behavioral response to others in a range of social contexts. Previous findings indicate the insular cortex (IC) and the nucleus accumbens (NAc) play important roles in social behaviors, and human neuroimaging implicates both IC and NAc in autism and other psychiatric disorders characterized by aberrant social cognition. To test whether IC projections to the NAc are involved in social decision-making, circuit-specific chemogenetic manipulations demonstrated that the IC → NAc pathway mediates social approach toward distressed juvenile, but not adult, conspecifics. This finding is the first to implicate this circuit in rodent socioemotional behaviors and may be a neuroanatomical substrate for integration of emotion with social reward.
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TL;DR
Bilateral pharmacological inhibition of nucleus accumbens core (NAc) abolished adult male rats’ preference for stressed juvenile (PN30) conspecifics but not avoidance of stressed adult (PN50) conspecifics. The insular cortex (IC)→NAc projection was necessary and sufficient for social approach to stressed juveniles, with greater Fos in NAc-projecting posterior IC neurons after interaction with stressed PN30 rats.
Key findings
- NAc inactivation with TTX (0.5 µl/side) blocked the preference for stressed PN30 conspecifics: vehicle-treated rats preferred stressed over naive PN30 (p = 0.006), while TTX-treated rats did not (p = 0.203). TTX did not alter PN50 avoidance: vehicle- and TTX-treated rats both preferred naive over stressed PN50 (p = 0.031 and p = 0.020, respectively).
- Social interaction with stressed PN30 conspecifics increased Fos immunoreactivity in IC→NAc neurons: main effect of conspecific stress F(1,16) = 16.89, p = 0.0008, with the only significant post hoc comparison in posterior IC (p = 0.015). Rats also showed more social exploration with stressed PN30 than naive PN30 conspecifics (t(10) = 3.281, p = 0.008).
- Chemogenetic inhibition of IC terminals in NAc blocked preference for stressed PN30 conspecifics: vehicle-treated rats preferred stressed PN30 (p = 0.023), while CNO-treated rats did not (p = 0.959); preference scores were reduced by CNO (t(9) = 2.089, p = 0.033). This manipulation did not alter PN50 avoidance (main effect of stress p = 0.003; preference score effect of CNO t(9) = 0.57, p = 0.293).
- Chemogenetic activation of IC terminals in NAc increased social exploration with PN30 conspecifics (CNO vs vehicle p = 0.030) but not PN50 conspecifics (p = 0.998). IC inhibition did not affect social novelty preference (main effect of familiarity p = 0.005; CNO effect p = 0.27).
Methods
- Male Sprague Dawley rats were used: experimental adults at PN60–PN80, juvenile conspecifics at PN30, and adult conspecifics at PN50. In the social affective preference (SAP) test, experimental rats explored two novel conspecifics for 5 min, one stressed via two foot shocks (5 s, 1 mA, 60 s intershock interval) and one naive; social exploration was scored by blinded observers.
- Surgeries included bilateral NAc cannula implantation, viral microinjections into posterior IC (hM4Di, hM3Dq, or mCherry), and unilateral NAc injection of retrograde tracer CTb488. Drugs included TTX infused into NAc, CNO given intraperitoneally or infused into NAc, and vehicle controls. Fos/mCherry immunohistochemistry and cell counting were used, with whole-cell electrophysiology to verify hM4Di and hM3Dq efficacy.
- Analyses used two-way ANOVAs, t tests, mixed-model ANOVAs, preference scores, and Sidak post hoc comparisons in Prism 8.2; effect sizes reported as η² or partial η². Sample sizes were based on a priori power analysis with a minimum of eight subjects per treatment condition.
Limitations
- The paper states that the retrograde Fos experiment had a small sample size and may have been underpowered to detect smaller effects of conspecific stress on IC→NAc neurons in anterior IC; future studies are needed to directly address whether these projections are involved in social approach behavior.
- The paper states that it cannot be sure approach to stressed juveniles is a prosocial response.
- Evident from the text: only male rats were studied, so sex differences are not addressed; some Fos-count groups had n = 3 or 4 observations per group.
Model-written summary. Check it against the paper before relying on it.
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- Findingown data
Chemogenetic inhibition of the IC-to-NAc tract blocked the preference to investigate stressed PN30 conspecifics.
“chemogenetic inhibition of this tract blocked the preference to investigate stressed PN30 conspecifics”
Quote in the paperSubstantial claim - Findingown data
Social interactions with stressed PN30 conspecifics elicit greater Fos immunoreactivity in IC-to-NAc neurons than interactions with naive PN30 conspecifics.
“Using a combination of retrograding tracing and c-Fos immunohistochemistry, we report that social interactions with stressed PN30 conspecifics elicit greater Fos immunoreactivity in IC ¡ NAc neurons than interactions with naive PN30 conspecifics.”
Quote in the paperSubstantial claim - Findingown data
A two-way ANOVA revealed a main effect of ROI on Fos-positive cells.
“Proceeding to the Fos analyses, a 2-way ANOVA revealed a main effect of ROI (F (2,10) ϭ 30.53, p Ͻ 0.0001).”
Quote in the paperNot a substantial claim - Findingcitation
Experimental rats displayed higher levels of social exploration with stressed PN30 conspecifics compared with naive PN30 conspecifics.
“As previously reported (Rogers-Carter et al., 2018b), experimental rats displayed higher levels of social exploration with stressed PN30 conspecifics compared with naive PN30 conspecifics (t (10) ϭ 3.281, p ϭ 0.008, 2 ϭ 0.52; Fig. 2D).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rogers-Carter et al., 2018b
Not checked in the free run.
- Findingown data
Anterior IC had significantly more CTb488-positive cells than medial or posterior IC.
“Anterior IC had significantly more CTb 488 -positive cells than medial or posterior IC ( p Ͻ 0.001; Fig. 2F ).”
Quote in the paperNot a substantial claim
- Findingown data
Preference scores from experimental rats tested with PN30 conspecifics were significantly greater in vehicle trials than TTX trials.
“Preference scores from experimental rats tested with PN30 conspecifics were significantly greater in vehicle trials than TTX trials ( p Ͻ 0.0001).”
Quote in the paperSubstantial claim - Findingown data
The interaction between conspecific stress and drug approached significance in the IC→NAc terminal inhibition experiment.
“an interaction between conspecific stress and drug approached significance (F (1,9) ϭ 4.214, p ϭ 0.070, P 2 ϭ 0.09).”
Quote in the paperNot a substantial claim - Findingown data
There was a significant conspecific stress × drug interaction in the SAP test after vehicle or CNO in hM4Di-transduced rats.
“This produced a significant conspecific stress ϫ drug interaction (F (1,9) ϭ 34.22, p ϭ 0.0002, P 2 ϭ 0.23).”
Quote in the paperSubstantial claim - Findingown data
At each dose of CNO (0, 0.3, 3.0 mg/kg), experimental rats spent more time exploring stressed PN30 conspecifics than naive.
“Post hoc comparisons further revealed that, at each dose, experimental rats spent more time exploring the stressed PN30 conspecifics than the naive (0 mg/kg, p ϭ 0.0009; 0.3 mg/kg, p ϭ 0.0036; 3.0 mg/kg, p ϭ 0.0063).”
Quote in the paperSubstantial claim - Findingown data
In the CNO condition, experimental rats did not exhibit preference for either the naive or stressed conspecific.
“In the CNO condition, experimental rats did not exhibit preference for either the naive or stressed conspecific ( p ϭ 0.959; Fig. 4E).”
Quote in the paperSubstantial claim - Findingown data
Experimental rats preferred to explore the stressed PN30 conspecific in both vehicle and CNO conditions in the no-virus control.
“Experimental rats preferred to explore the stressed PN30 conspecific in both the vehicle ( p ϭ 0.003) and CNO ( p ϭ 0.031) conditions (Fig. 4G)”
Quote in the paperSubstantial claim - Findingown data
There was a main effect of Conspecific Stress on CTb 488 and Fos-positive co-labeled neurons.
“we report a main effect of Conspecific Stress (F (1,16) ϭ 16.89, p ϭ 0.0008).”
Quote in the paperSubstantial claim - Findingown data
In adult SAP tests, test rats spent more time interacting with the naive conspecific after both vehicle and drug conditions.
“In adult SAP tests, test rats spent more time interacting with the naive conspecific after both vehicle and drug conditions.”
Quote in the paperNot a substantial claim - Findingown data
Rats with sham mCherry virus spent more time exploring stressed PN30 conspecific after both vehicle and CNO treatment.
“Rats spent more time exploring the stressed PN30 conspecific after both vehicle ( p ϭ 0.003) and CNO ( p ϭ 0.002) treatment (Fig. 3F )”
Quote in the paperSubstantial claim - Findingown data
More Fos-positive cells were found in anterior IC than in medial or posterior IC.
“More Fos-positive cells were found in anterior IC, than medial or posterior IC (ps Ͻ 0.001; Fig. 2G)”
Quote in the paperNot a substantial claim - Findingown data
The only significant post hoc comparison for CTb 488 and Fos-positive co-labeled neurons was between naive and stressed conspecific groups in the posterior IC.
“the only significant post hoc comparison was observed between naive and stressed conspecific groups in the posterior IC ( p ϭ 0.015; Fig. 2H ).”
Quote in the paperSubstantial claim - Findingown data
Vehicle-treated rats spent more time exploring stressed PN30 conspecifics than naive PN30 conspecifics.
“Vehicletreated rats spent more time exploring stressed PN30 conspecifics than naive PN30 conspecifics ( p ϭ 0.0001; Fig. 3F ).”
Quote in the paperSubstantial claim - Findingown data
Avoidance of stressed PN50 conspecifics was maintained after TTX treatment.
“This reflects that avoidance of stressed PN50 conspecifics was maintained after TTX treatment (Fig. 1F ).”
Quote in the paperSubstantial claim - Findingown data
There was a main effect of conspecific stress in rats without virus transduction given CNO at 0, 0.3, and 3.0 mg/kg.
“A two-way ANOVA with conspecific stress and dose as withinsubjects factors revealed a main effect of conspecific stress (F (1,7) ϭ 62.93, p ϭ 0.0001, p 2 ϭ 0.45).”
Quote in the paperSubstantial claim - Findingown data
TTX did not alter preference scores in experimental rats tested with PN50 conspecifics.
“However, TTX did not alter preference scores in experimental rats tested with PN50 conspecifics ( p ϭ 0.651).”
Quote in the paperSubstantial claim - Findingown data
In rats transduced with hM4Di, administration of CNO attenuated the preference for the stressed conspecific.
“In rats with transduced with hM4Di, administration of CNO attenuated the preference for the stressed conspecific (t (9) ϭ 5.654, p ϭ 0.0003, 2 ϭ 0.78).”
Quote in the paperSubstantial claim - Findingown data
There was a main effect of Conspecific Stress on social exploration time in the IC→NAc terminal inhibition experiment.
“A 2-way ANOVA of social exploration time revealed a main effect of Conspecific Stress (F (1,9) ϭ 16.28, p ϭ 0.003, p 2 ϭ 0.12)”
Quote in the paperSubstantial claim - Findingown data
There were no significant differences in Fos between conspecific stress groups.
“there were no significant differences in Fos between conspecific stress groups.”
Quote in the paperNot a substantial claim - Findingown data
There was a main effect of drug and conspecific stress in rats without virus administration given vehicle or CNO in NAc.
“A two-way ANOVA revealed a main effect of drug (F (1,6) ϭ 15.48, p ϭ 0.008, P 2 ϭ 0.04) and conspecific stress (F (1,6) ϭ 34.78, p ϭ 0.001, P 2 ϭ 0.40).”
Quote in the paperSubstantial claim - Findingown data
In the vehicle condition, experimental rats preferred to explore the stressed PN30 conspecific over the naive.
“In the vehicle condition, experimental rats preferred to explore the stressed PN30 conspecific over the naive ( p ϭ 0.023).”
Quote in the paperSubstantial claim - Findingown data
Greater Fos immunoreactivity in NAc-projecting posterior IC neurons was evident in experimental rats after social interactions with stressed PN30 conspecifics compared with naive PN30 conspecifics.
“Greater Fos immunoreactivity in NAc-projecting posterior IC neurons was evident in experimental rats after social interactions with stressed PN30 conspecifics compared with naive PN30 conspecifics.”
- Also stated in: § Discussion · plain
“we observed greater Fos IC ¡ NAc neurons after interactions with stressed juveniles, with the greatest difference observed in the posterior IC.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
CNO-treated rats expressed greater Fos-immunoreactivity compared with vehicle-treated rats in NAc.
“CNO-treated rats expressed greater Fos-immunoreactivity compared with vehicle-treated rats (t (5) ϭ 2.727, p ϭ 0.041, 2 ϭ 0.60; Fig. 5H )”
Quote in the paperSubstantial claim - Findingown data
There were main effects of conspecific age and drug on social exploration in the activation experiment.
“This analysis revealed main effects of conspecific age (F (1,6) ϭ 6.568, p ϭ 0.043, P 2 ϭ 0.52) and drug (F (1,6) ϭ 12.80, p ϭ 0.012, P 2 ϭ 0.68).”
Quote in the paperSubstantial claim - Findingown data
CNO had no effect on social novelty preference.
“CNO had no effect on social novelty preference ( p ϭ 0.27).”
Quote in the paperSubstantial claim - Findingown data
Experimental rats spent significantly more time exploring the unfamiliar conspecific in the social novelty preference test.
“Experimental rats (n ϭ 10) spent significantly more time exploring the unfamiliar conspecific (t (9) ϭ 3.703, p ϭ 0.005, P 2 ϭ 0.60).”
- Also stated in: § Discussion · plain
“Experimental rats spent significantly more time investigating the unfamiliar target.**p ϭ 0.005.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
There was a main effect of familiarity on social novelty preference.
“A repeated-measures ANOVA revealed a main effect of familiarity (F (1,6) ϭ 19.12, p ϭ 0.005, p 2 ϭ 0.22)”
- Also stated in: § Discussion · plain
“Experimental rats preferred interaction with the unfamiliar conspecific under both injection conditions (**main effect of familiarity, p ϭ 0.005).”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
There was a main effect of conspecific stress in adult SAP tests.
“A two-way ANOVA revealed a main effect of conspecific stress (F (1,8) ϭ 16.77, p ϭ 0.003, p 2 ϭ 0.24).”
Quote in the paperNot a substantial claim - Findingown data
Converting adult SAP results to percentage preference scores revealed no effect of CNO.
“Converting these results to percentage preference scores revealed no effect of CNO (t (9) ϭ 0.57, p ϭ 0.293).”
Quote in the paperNot a substantial claim - Findingown data
Chemogenetic inhibition of the IC did not alter social approach to a novel conspecific.
“Interestingly, chemogenetic inhibition of the IC did not alter social approach to a novel conspecific.”
Quote in the paperNot a substantial claim - Findingown data
More Fos-positive cells were observed in anterior IC than medial or posterior IC.
“More Fos-positive cells were observed in anterior IC than medial or posterior ( p Ͻ 0.0001)”
Quote in the paperNot a substantial claim- Rests on an assumption: Fos immunoreactivity reflects neuronal activity.
- Findingown data
There was no effect of conspecific stress on the number of Fos-positive cells at any ROI.
“there was no effect of conspecific stress on the number of Fos-positive cells at any ROI.”
Quote in the paperNot a substantial claim- Rests on an assumption: Fos immunoreactivity reflects neuronal activity.
- Findingown data
No dose of CNO disrupted the preference for the stressed PN30 conspecific in control rats without viral transduction.
“No dose of CNO disrupted the preference for the stressed PN30 conspecific (0 mg/kg, p ϭ 0.0009; 0.3 mg/kg, p ϭ 0.0036 mg/kg; 3 mg/kg, p ϭ 0.0063).”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Findingown data
Chemogenetic inhibition of IC blocked the social affective preference for stressed PN30 conspecifics.
“Chemogenetic inhibition of IC blocked the social affective preference for stressed PN30 conspecifics.”
- Also stated in: § Discussion · plain
“Vehicle-treated rats spent more time exploring the stressed PN30 conspecifics than the naive PN30 ( p ϭ 0.0001), which was abolished in trials after injections of CNO (3 mg/kg, i.p.) 45 min before testing ( p ϭ 0.517).”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Also stated in: § Discussion · plain
- Findingown data
Exposure to stressed PN30 conspecifics elicited greater Fos immunoreactivity in IC→NAc neurons than exposure to naive PN30 conspecifics.
“Exposure to stressed PN30 conspecifics elicited greater Fos immunoreactivity in IC ¡ NAc neurons than exposure to naive PN30 conspecifics.”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Rests on an assumption: Fos immunoreactivity reflects neuronal activity.
- Rests on an assumption: CTb488 retrogradely labels NAc-projecting IC neurons.
- Findingown data
Experimental rats transduced with a sham virus preferred to explore the stressed PN30 conspecific under vehicle and 3 mg/kg CNO.
“Experimental rats transduced with a sham virus (n ϭ 9) preferred to explore the stressed PN30 conspecific under vehicle ( p ϭ 0.003) and 3 mg/kg CNO (i.p.) ( p ϭ 0.002).”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Findingown data
Bilateral infusion of TTX (100 nM, 0.5 μl/side) into NAc 15 min before testing abolished the social affective preference for stressed PN30 conspecifics.
“Pharmacological inhibition of the NAc abolished the social affective preference for stressed PN30, but not PN50, conspecifics.”
- Also stated in: § Discussion · plain
“which was abolished via bilateral infusion ofTTX (100 nM, 0.5 l/side) in NAc 15 min before testing ( p ϭ 0.203).”
Quote in the paperSubstantial claim- Rests on an assumption: TTX infusion in NAc inactivates NAc neurons without affecting adjacent regions.
- Also stated in: § Discussion · plain
- Findingown data
There was no effect of conspecific stress on the number of CTb488-positive cells at any ROI.
“there was no effect of conspecific stress on the number of CTb 488 -positive cells at any ROI.”
Quote in the paperNot a substantial claim- Rests on an assumption: CTb488 retrogradely labels NAc-projecting IC neurons.
- Findingown data
A main effect of stress was observed on colabeled CTb488 and Fos-positive neurons.
“A main effect of stress was observed ( p ϭ 0.0008)”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Rests on an assumption: Fos immunoreactivity reflects neuronal activity.
- Rests on an assumption: CTb488 retrogradely labels NAc-projecting IC neurons.
- Findingown data
Bilateral infusion of TTX into NAc did not affect the preference for naive PN50 conspecifics.
“Pharmacological inhibition of the NAc abolished the social affective preference for stressed PN30, but not PN50, conspecifics.”
- Also stated in: § Discussion · plain
“Rats tested with PN50 conspecifics show a preference for naive conspecifics, which was unaffected by TTX treatment ( p ϭ 0.452).”
- Also stated in: § Discussion · plain
“Both vehicle-treated ( p ϭ 0.031) and TTX-treated ( p ϭ 0.020) rats preferred to explore naive PN50 conspecifics compared with the stressed PN50 conspecifics.”
Quote in the paperSubstantial claim- Rests on an assumption: TTX infusion in NAc inactivates NAc neurons without affecting adjacent regions.
- Also stated in: § Discussion · plain
- Findingown data
The only condition in which CNO reduced the preference for the stressed PN30 conspecific was in experimental rats transduced with hM4D(Gi).
“The only condition in which CNO reduced the preference for the stressed PN30 conspecific was in experimental rats transduced with hM4D(Gi) ( p ϭ 0.0003).”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Findingown data
Vehicle-treated rats preferred to explore stressed PN30 conspecifics compared with naive PN30 conspecifics.
“Vehicle-treated rats preferred to explore stressed PN30 conspecifics compared with naive PN30 conspecifics ( p ϭ 0.006)”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Findingown data
Experimental rats that explored stressed PN30 conspecifics expressed more Fos immunoreactivity in CTb488-positive neurons in posterior IC compared with experimental rats who explored naive PN30 conspecifics.
“experimental rats that explored stressed PN30 conspecifics expressed more Fos immunoreactivity in CTb 488 -positive neurons in posterior IC ( p ϭ 0.015) compared with experimental rats who explored naive PN30 conspecifics.”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Rests on an assumption: Fos immunoreactivity reflects neuronal activity.
- Rests on an assumption: CTb488 retrogradely labels NAc-projecting IC neurons.
- Findingown data
Both vehicle-treated and TTX-treated rats preferred to explore naive PN50 conspecifics compared with stressed PN50 conspecifics.
“Both vehicle-treated ( p ϭ 0.031) and TTX-treated ( p ϭ 0.020) rats preferred to explore naive PN50 conspecifics compared with the stressed PN50 conspecifics.”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Findingown data
Experimental rats presented stressed PN30 conspecifics engaged in more social exploration than rats presented naive PN30 conspecifics.
“Experimental rats presented stressed PN30 conspecifics engaged in more social exploration than rats presented naive PN30 conspecifics ( p ϭ 0.008).”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Findingown data
More CTb488-positive cells were observed in anterior IC than medial or posterior IC.
“More CTb 488 -positive cells were observed in anterior IC than medial or posterior IC ( p Ͻ 0.0001)”
Quote in the paperNot a substantial claim- Rests on an assumption: CTb488 retrogradely labels NAc-projecting IC neurons.
- Findingown data
Insular cortex inhibition does not affect social novelty preference.
“Insular cortex inhibition does not affect social novelty preference.”
Quote in the paperSubstantial claim - Findingown data
Percentage preference scores for the stressed conspecific did not differ between vehicle and drug groups for PN50.
“scores did not differ between vehicle and drug groups.”
Quote in the paperNot a substantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Findingown data
Experimental rats preferred interaction with the unfamiliar conspecific under both vehicle and CNO injection conditions.
“Experimental rats preferred interaction with the unfamiliar conspecific under both injection conditions (**main effect of familiarity, p ϭ 0.005).”
Quote in the paperSubstantial claim - Findingown data
Experimental rats spent significantly more time investigating the unfamiliar target.
“Experimental rats spent significantly more time investigating the unfamiliar target.**p ϭ 0.005.”
Quote in the paperSubstantial claim - Findingown data
Chemogenetic excitation of IC terminals in NAc did not affect social exploration with PN50 conspecifics.
“Chemogenetic excitation of IC terminals in NAc increased social exploration with PN30, but not PN50, conspecifics.”
- Also stated in: § Discussion · plain
“whereas social exploration with PN50 conspecifics was unaffected by drug treatment ( p ϭ 0.998).”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Also stated in: § Discussion · plain
- Findingown data
After 10 min of bath application, CNO increased the number of action potentials evoked by current injection in hM3Dq-mCherry-positive neurons in the IC.
“After 10 min of bath application, CNO increased the number of action potentials evoked by current injection in hM3Dq-mCherry-positive neurons in the IC.”
Quote in the paperSubstantial claim - Findingown data
Chemogenetic excitation of IC terminals in NAc increased social exploration with PN30 conspecifics.
“Chemogenetic excitation of IC terminals in NAc increased social exploration with PN30, but not PN50, conspecifics.”
- Also stated in: § Discussion · plain
“Experimental rats spent more time exploring naive PN30 conspecifics after CNO injections than after vehicle treatment ( p ϭ 0.030)”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Also stated in: § Discussion · plain
- Findingown data
Chemogenetic inhibition of IC→NAc terminals blocked the social affective preference for stressed PN30 conspecifics.
“Chemogenetic inhibition of IC ¡ NAc terminals blocked the social affective preference for stressed PN30 conspecifics.”
- Also stated in: § Discussion · plain
“Vehicle-treated rats spent more time exploring the stressed PN30 conspecifics than the naive PN30 conspecifics ( p ϭ 0.023), which was abolished via 1 M CNO injections 45 min before testing through the guide cannula.”
- Also stated in: § Discussion · plain
“Experimental rats show a preference to explore the stressed conspecific under vehicle treatment, which was significantly reduced after pharmacological inhibition of IC terminals in NAc in CNO ( p ϭ 0.033).”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Also stated in: § Discussion · plain
- Findingown data
After 10 min of bath application, CNO reduced the number of action potentials evoked by current injection in hM4D(Gi)-mCherry-positive neurons in the IC.
“After 10 min of bath application, CNO reduced the number of action potentials evoked by current injection in hM4D(Gi)-mCherry-positive neurons in the IC.”
Quote in the paperSubstantial claim - Findingown data
Test rats spent more time exploring the naive conspecifics than the stressed PN50 conspecifics regardless of injection.
“Test rats spent more time exploring the naive conspecifics than the stressed PN50 conspecifics regardless of injection (main effect of stress, p ϭ 0.003).”
Quote in the paperNot a substantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
- Findingown data
Greater NAc Fos immunoreactivity was observed in rats injected with CNO before perfusion compared with rats treated with vehicle.
“Greater NAc Fos immunoreactivity was observed in rats injected with CNO before perfusion compared with rats treated with vehicle ( p ϭ 0.041).”
Quote in the paperSubstantial claim- Rests on an assumption: Fos immunoreactivity reflects neuronal activity.
- Premiseown data
The social affective preference pattern depends upon the insular cortex (IC).
“This pattern depends upon the insular cortex (IC), which is anatomically connected to the nucleus accumbens core (NAc).”
- Also stated in: § Introduction · plain
“Optogenetic silencing of IC pyramidal neurons abolished this pattern.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rogers-Carter et al., 2018b
Not checked in the free run.
- Also stated in: § Introduction · plain
- Interpretationown data
Outputs of IC to the NAc modulate social approach.
“These new findings suggest that outputs of IC to the NAc modulate social approach, which provides new insight to the neural circuitry underlying social decision-making.”
Quote in the paperSubstantial claim - Premisecitation
The IC is highly interconnected with the social decision-making network.
“it is highly interconnected with the social decision-making network positioning it as a hub for socioemotional information to be incorporated in social decision-making processes (Rogers-Carter and Christianson, 2019).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rogers-Carter and Christianson, 2019
Not checked in the free run.
- Premisecitation
The NAc is a major target of IC afferents.
“IC provides a major cortical input to the NAc (Wright and Groenewegen, 1996).”
- Also stated in: § Exposure to stressed PN30 conspecifics activated IC neurons that project to NAc · plain
“The NAc is a major target of IC afferents (Wright and Groenewegen, 1996)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wright and Groenewegen, 1996
Not checked in the free run.
- Also stated in: § Exposure to stressed PN30 conspecifics activated IC neurons that project to NAc · plain
- Interpretationown data
The effect of CNO observed in hM4Di expressing rats cannot be attributed to off-target effects of CNO on NAc function.
“which supports that the effect of CNO observed in hM4Di expressing rats cannot be attributed to off target effects of CNO on NAc function.”
Quote in the paperSubstantial claim - Premisecitation
Preference to explore stressed PN30 and naive PN50 conspecifics was mediated by IC using an optogenetic approach.
“We previously reported (Rogers-Carter et al., 2018b) that the preference to explore stressed PN30 and naive PN50 conspecifics was mediated by IC using an optogenetic approach.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rogers-Carter et al., 2018b
Not checked in the free run.
- Interpretationown data
i.p. injections of CNO at 0.3 or 3.0 mg/kg per se did not interfere with social affective preference behavior.
“These findings demonstrate that i.p. injections of CNO at 0.3 or 3.0 mg/kg per se did not interfere with social affective preference behavior (Fig. 3G,H ).”
Quote in the paperSubstantial claim - Interpretationown data
Manipulations of this tract did not influence behavior between two adult conspecifics.
“Interestingly, manipulations of this tract did not influence behavior between two adult conspecifics.”
Quote in the paperSubstantial claim - Interpretationown data
Chemogenetic inhibition of IC→NAc terminals appears insufficient to alter preference for the naive rat in adult SAP tests.
“Consistent with the lack of effect of TTX in the NAc on adult SAP, chemogenetic inhibition of the IC ¡ NAc terminals appears to be insufficient to alter preference for the naive rat in adult SAP tests.”
Quote in the paperSubstantial claim - Premisecitation
Like NAc, IC output neurons are necessary for the social affective preference for the stressed juvenile.
“Like NAc, IC output neurons are necessary for the social affective preference for the stressed juvenile (Rogers-Carter et al., 2018b).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rogers-Carter et al., 2018b
Not checked in the free run.
- Interpretationcitation
In the SAP paradigm, the preference to explore stressed juveniles may be mediated by the NAc because this region integrates the valence of conspecific affect with reward valuation.
“In the SAP paradigm, the preference to explore stressed juveniles may be mediated by the NAc because this region integrates the valence of conspecific affect with reward valuation (Hamel et al., 2017).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Hamel et al., 2017
Not checked in the free run.
- Interpretationown data
IC projections to NAc are necessary to show a preference to explore the stressed PN30 conspecific compared with the naive PN30.
“Together, these results indicate that IC projections to NAc are necessary to show a preference to explore the stressed PN30 conspecific compared with the naive PN30.”
Quote in the paperSubstantial claim - Interpretationown data
During interactions with stressed juveniles, IC projections to NAc mediate the increase in social investigation directed toward the stressed targets.
“The results reviewed thus far suggest that during interactions with stressed juveniles IC projections to the NAc mediate the increase in social investigation directed toward the stressed targets.”
Quote in the paperSubstantial claim - Interpretationown data
These results implicate the IC→NAc pathway in prosocial behaviors directed toward juveniles.
“These results implicate the IC ¡ NAc pathway in prosocial behaviors directed toward juveniles.”
Quote in the paperSubstantial claim- Rests on an assumption: Approach to stressed juveniles is a prosocial response.
- Interpretationown data
These findings demonstrate the modulatory role of IC→NAc projections on social approach in a preference paradigm.
“Together, these findings demonstrate the modulatory role of IC ¡ NAc projections on social approach in a preference paradigm.”
Quote in the paperSubstantial claim - Interpretationown data
Our results provide mechanistic support for this axis as a key to normative social cognition.
“Our results provide mechanistic support for this axis as a key to normative social cognition.”
Quote in the paperSubstantial claim - Study design and conductown data
IC pAAV5-hSyn-hM3D(Gq)-mCherry expression was confirmed in experimental rats (n=7).
“Map of cannula tip placements in NAc (left) and IC pAAV5-hSyn-hM3D(Gq)-mCherry expression in experimental rats (right).Each subject is represented by a different color (n ϭ 7).”
Quote in the paperSubstantial claim - Study design and conductown data
Bilateral IC pAAV5-hSyn-hM4D(Gi)-mCherry expression was confirmed in experimental rats (n=10).
“Map of bilateral IC pAAV5-hSyn-hM4D(Gi)-mCherry expression in experimental rats.Each subject is represented in a different color (n ϭ 10)”
Quote in the paperSubstantial claim
- May combine two claims. 40
- Classified as probably not a substantial claim. 49
May combine two claims.
Findingown dataBilateral pharmacological inhibition of the NAc with tetrodotoxin abolishes the preference for stressed PN30 conspecifics but does not alter interactions with PN50 conspecifics.
“Bilateral pharmacological inhibition of the NAc with tetrodotoxin (1 M; 0.5 l/side) abolished the preference for stressed PN30, but did not alter interactions with PN50 conspecifics.”
- Also stated in: § Pharmacological inactivation of NAc abolished preference for stressed PN30, but not PN50, conspecifics · boosted
“These analyses demonstrate that the NAc is necessary for experimental rats' preference to explore stressed PN30 but did not influence interactions with either stressed or naive PN50, conspecifics.”
- Also stated in: § Pharmacological inactivation of NAc abolished preference for stressed PN30, but not PN50, conspecifics · plain
“After vehicle treatment, rats tested with PN30 conspecifics showed a preference to explore the stressed conspecific over the naive ( p ϭ 0.006), which was abolished after bilateral pharmacological inactivation of NAc ( p ϭ 0.203; Fig. 1D).”
Quote in the paperSubstantial claim- Also stated in: § Pharmacological inactivation of NAc abolished preference for stressed PN30, but not PN50, conspecifics · boosted
May combine two claims.
Findingown dataChemogenetic stimulation of IC terminals in the NAc increased social exploration with juvenile, but not adult, conspecifics.
“Chemogenetic stimulation of IC terminals in the NAc increased social exploration with juvenile, but not adult, conspecifics”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn PN50 tests, rats preferred the naive conspecific over the stressed conspecific after vehicle treatment, and this preference was maintained after TTX treatment.
“For rats tested with PN50 conspecifics, a two-way ANOVA found a main effect of conspecific affect (F (1,6) ϭ 5.45, p ϭ 0.058, P 2 ϭ 0.30), which confirmed replication our previous findings (Rogers-Carter et al., 2018a,b) that experimental rats prefer to explore the naive conspecific over the stressed after vehicle treatment ( p ϭ 0.031), which was also maintained after TTX treatment ( p ϭ 0.020;”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rogers-Carter et al., 2018a,b
Not checked in the free run.
May combine two claims.
Findingown dataBath application of 10 M CNO reliably hyperpolarized and reduced excitability of IC neurons visually identified as mCherry-positive at the time of recording.
“bath application of 10 M CNO reliably hyperpolarized and reduced excitability of IC neurons visually identified as mCherry-positive at the time of recording.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAdministration of CNO alone, or vehicle or CNO to rats with sham mCherry virus, did not disrupt baseline preference to explore stressed PN30 conspecific.
“In no instance did administration of CNO alone (F (7,14) ϭ 0.343, p ϭ 0.956, 2 Ͻ 0.01), or vehicle or CNO administration to rats with the sham mCherry virus (t (8) ϭ 0.010, p ϭ 0.992, h 2 Ͻ 0.01) disrupt the baseline preference to explore the stressed PN30 conspecific.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataPercentage preference scores reflected more time spent with the stressed conspecific after vehicle injections, which was reduced by CNO.
“experimental rats showed scores that reflected more time spent with the stressed conspecific after vehicle injections, which was reduced by CNO (t (9) ϭ 2.089, p ϭ 0.033, P 2 ϭ 0.33).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThere was a main effect of CNO and significantly fewer spikes under CNO compared with aCSF in slice recordings.
“A one-way repeatedmeasures ANOVA revealed a main effect of CNO (F (2,6) ϭ 6.038, p ϭ 0.040, 2 ϭ 0.66) and significantly fewer spikes under CNO compared with aCSF ( p ϭ 0.029).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe preference for stressed PN30 conspecifics was abolished after inhibition of IC neurons; CNO-treated rats did not show a preference for naive or stressed PN30 conspecific.
“This preference was abolished after inhibition of IC neurons as experimental rats tested with CNO did not show a preference for the naive or stressed PN30 conspecific ( p ϭ 0.517; Fig. 3F ).”
Quote in the paperSubstantial claimMay combine two claims.
FindingreasoningChemogenetic stimulation of IC terminals in NAc increased exploration with PN30, but not PN50, conspecifics.
“Accordingly, chemogenetic stimulation of IC terminals in NAc increased exploration with PN30, but not PN50, conspecifics.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataMean social exploration was greater with PN30 conspecifics after CNO treatment than vehicle, whereas mean social exploration with PN50 conspecifics did not differ between CNO and vehicle treatment.
“Post hoc comparisons show mean social exploration was greater with PN30 conspecifics after CNO treatment than vehicle ( p ϭ 0.030), whereas mean social exploration with PN50 conspecifics did not differ between CNO and vehicle treatment ( p ϭ 0.998) (Fig. 5H ).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThere was a small but significant effect of CNO on overall interaction levels in adult SAP tests.
“As in the CNO only experiment, there was a small but significant effect of CNO on overall interaction levels evinced by a main effect of drug (F (1,8) ϭ 5.45, p ϭ 0.047, P 2 ϭ 0.12).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn SAP tests, chemogenetic inhibition of this circuit blocked the preference for the stressed PN30 conspecific but had no apparent effect on avoidance of stressed PN50 conspecifics.
“In SAP tests, chemogenetic inhibition of this circuit blocked the preference for the stressed PN30 conspecific but had no apparent effect on avoidance of stressed PN50 conspecifics.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataPharmacological inactivation of NAc prevented the expected preference for test rats to explore stressed PN30 conspecifics, but did not alter avoidance of stressed PN50 conspecifics.
“First, pharmacological inactivation of the NAc prevented the expected preference for test rats to explore stressed PN30 conspecifics, but did not alter the avoidance of stressed PN50 conspecifics.”
- Also stated in: § Discussion · plain
“when NAc was pharmacologically inactivated with TTX, rats did not show a social preference for the stressed PN30 conspecific and thus behaved as if each conspecific was equal in valence.”
Quote in the paperSubstantial claim- Also stated in: § Discussion · plain
May combine two claims.
Findingown dataSham experimental rats without hM4D(Gi) transduction preferred to explore the stressed PN30 conspecifics under vehicle treatment, which was maintained after microinfusion of 1 μM CNO to the NAc 45 min before testing.
“Under vehicle treatment, rats preferred to explore the stressed PN30 conspecifics ( p ϭ 0.003), which was maintained after microinfusion of 1 M CNO to the NAc 45 min before testing (0.031).”
Quote in the paperSubstantial claim- Rests on an assumption: The conspecifics designated as stressed were indeed stressed.
May combine two claims.
PremisecitationAdult test rats prefer to interact with stressed juvenile (PN30) conspecifics but avoid stressed adult (PN50) conspecifics.
“Adult test rats prefer to interact with stressed juvenile (postnatal day 30, PN30) conspecifics but avoid stressed adult (PN50) conspecifics.”
- Also stated in: § Introduction · plain
“Specifically, in the SAP test, experimental rats exhibit approach toward stressed juvenile rats, but avoid exploring stressed adult rats.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rogers-Carter et al., 2018b
Not checked in the free run.
- Also stated in: § Introduction · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe initial sample sizes were determined by a priori power analysis using effect sizes from prior observations.
“The initial sample sizes for these experiments were determined by a priori power analysis (G*Power ver.3.1) using the effect sizes from our prior observations using repeated-measures designs.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductown dataFour animals, two from each stress group, did not exhibit CTb488 in the NAc and were excluded from all subsequent analysis.
“Four animals, two from each stress group, did not exhibit CTb 488 in the NAc and so were excluded from all subsequent analysis.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenExperimental treatments were counterbalanced in order and repeated-measures designs were used except when noted.
“Experimental treatments were counterbalanced in order and repeated-measures designs were used except when noted.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenBefore analysis, all data were visually inspected for normality and order effects.
“Before analysis, all data were visually inspected for normality and order effects.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenFos-immunoreactive cells were manually counted in ImageJ by an observer blind to treatment.
“Fos-immunoreactive cells were manually counted in ImageJ by an observer blind to treatment.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataIn all cases, the data were deemed suitable for parametric analysis.
“In all cases, the data were deemed suitable for parametric analysis and all data are depicted in the figures.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationInsula projections to the NAc are most dense in the anterior IC compared with the posterior IC.
“It is established that the insula projections to NAc is most dense in the anterior IC, compared with the posterior IC (Parks et al., 2015) and this trend was evident and supported by a significant main effect of ROI (F (2,16) ϭ 19.3, p Ͻ 0.0001).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Parks et al., 2015
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductnone givenAll data were included unless cannula implants or virus transduction missed the target site.
“All data were included unless cannula implants or virus transduction missed the target site.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe correlation between observers for the SAP trials was r=0.922, R2=0.849, p<0.0001.
“The correlation between observers for the SAP trials included in the current experiments was r 35 ϭ 0.922, R 2 ϭ 0.849, p Ͻ 0.0001.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataCounts were unavailable from one subject from each treatment group at the anterior IC and medial IC regions, resulting in n=3 or 4 observations per group.
“We were unable to obtain counts from one subject from each treatment group at the anterior IC and medial IC regions resulting in n ϭ 3 or 4 observations per group.”
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 dataA trained observer blinded to treatment quantified social exploration, and a second observer blind to experimental conditions re-quantified from video to establish interrater reliability.
“A trained observer blinded to treatment quantified the amount of social exploration initiated by the experimental rat”
- Also stated in: § Subjects. · plain
“Social exploration was quantified first during live testing and again from digital video recordings by a second observer who was blind to experimental conditions to establish interraterreliability.”
Quote in the paperNot a substantial claim- Also stated in: § Subjects. · plain
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataThe correlation between observers for the social interaction tests was r=0.997, R2=0.993, p<0.0001.
“The correlation between observers for the social interaction tests included in the current experiments was r 12 ϭ 0.997, R 2 ϭ 0.993, p Ͻ 0.0001.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataPilot studies found no evidence of treatment order effects on SAP behavior when using tetrodotoxin or CNO injections.
“We tested for order effects in pilot studies and did not find evidence of treatment order effects on SAP behavior when using tetrodotoxin or CNO injections (either intraperitoneal or intracranial administration).”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataThe IC-to-NAc tract is necessary and sufficient for approach toward stressed juvenile conspecifics, but not avoidance of stressed adult conspecifics.
“We report that this tract is necessary and sufficient for approach toward stressed juvenile conspecifics, but not avoidance of stressed adult conspecifics.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataCTb488 and Fos-positive colabeled cells were manually counted in ImageJ by a trained observer blinded to treatment.
“CTb 488 and Fos-positive colabeled cells were manually counted in ImageJ by a trained observer blinded to treatment.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationThe NAc encodes ultrasonic vocalization calls that convey stress and shows enhanced dopaminergic transmission in subjects that observe a conspecific receiving foot shock.
“NAc encodes ultrasonic vocalization calls that convey stress (Willuhn et al., 2014) and shows enhanced dopaminergic transmission in subjects that observe a conspecific receiving foot shock (Wu et al., 1999)”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Willuhn et al., 2014
Not checked in the free run.
- cites Wu et al., 1999
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThe nucleus accumbens core (NAc) is implicated in reward.
“The nucleus accumbens core (NAc) is implicated in reward (Wise, 2002)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wise, 2002
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRodents demonstrate either prosocial or avoidance behaviors toward distressed others.
“a number of studies report that rodents demonstrate either prosocial or avoidance behaviors toward distressed others (reviewed by (Meyza et al., 2017).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Meyza et al., 2017
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThe insular cortex (IC) is a site of multisensory integration.
“The insular cortex (IC) is a site of multisensory integration (Rodgers et al., 2008;Gogolla et al., 2014;Gogolla, 2017)”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Rodgers et al., 2008
Not checked in the free run.
- cites Gogolla et al., 2014
Not checked in the free run.
- cites Gogolla, 2017
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe NAc mediates social recognition and reward with juvenile and adult conspecifics.
“NAc mediates social recognition (Ploeger et al., 1991) and reward with juvenile (Trezza et al., 2011) and adult conspecifics (Do ¨len et al., 2013).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Ploeger et al., 1991
Not checked in the free run.
- cites Trezza et al., 2011
Not checked in the free run.
- cites Dölen et al., 2013
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationResponses to distressed others are modulated by situational factors, including familiarity, age, social rank, sex and prior experience.
“These responses are modulated by situational factors, including familiarity, age, social rank, sex and prior experience (Langford et al., 2006;Guzma ´n et al., 2009;Ishii et al., 2012;Kiyokawa et al., 2014;Li et al., 2014;Burkett et al., 2016;Meyza et al., 2017;Rogers-Carter et al., 2018a,b)”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Langford et al., 2006
Not checked in the free run.
- cites Guzmán et al., 2009
Not checked in the free run.
- cites Ishii et al., 2012
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataTwo experimental rats were excluded due to lack of virus expression.
“Two experimental rats were excluded due to lack of virus expression.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataExposure to stressed conspecifics led to greater activity in NAc-projecting IC neurons, with the greatest differential activation observed in the posterior subregion of IC.
“In sum, exposure to stressed conspecifics led to greater activity in NAc-projecting IC neurons with the greatest differential activation observed in the posterior subregion of IC.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataRats were only included in the final analysis if there was positive evidence of virus expression in IC, bilateral cannula tip placement in NAc, and mCherry immunoreactivity of putative IC axon terminals in NAc.
“Rats were only included in the final analysis if there was positive evidence of virus expression in IC as in Figure 4A, right; map of virus expression in Figure 4B, bilateral cannula tip placement in NAc (Fig. 4A, right, map in Fig. 4C), and mCherry immunoreactivity of putative IC axon terminals in NAc (Fig. 4A, right inset).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenOnly rats meeting criteria for IC hM4D(Gi) expression, bilateral NAc cannula placement, mCherry expression in NAc, and avoidance of the stressed conspecific under vehicle conditions were included in analysis.
“Only rats meeting the criteria for IC hM4D(Gi) expression, bilateral NAc cannula placement, mCherry expression in NAc, and avoidance of the stressed conspecific under vehicle conditions were included in analysis.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe IC→NAc track is necessary and sufficient for social approach under conditions with a juvenile conspecific.
“The foregoing results suggest the IC ¡ NAc track is necessary and sufficient for social approach under conditions with a juvenile conspecific.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThree rats were excluded due to misplaced cannula or lack of virus expression.
“Three rats were excluded due to misplaced cannula or lack of virus expression.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataFor each experimental rat included in the analysis, virus transduction, cannula tip location in NAc, and presence of terminal fibers expressing mCherry in NAc were confirmed.
“For each experimental rat included in the analysis, we confirmed the virus transduction via fluorescent imaging of the mCherry reporter (Fig. 5 A, C, right), the location of the cannula tips in NAc (Fig. 5 B, C), and the presence of terminal fibers expressing mCherry in NAc (Fig. 5B, inset).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataExcitation of IC terminals in NAc via CNO was sufficient to increase exploration with PN30, but not PN50, conspecifics.
“These results indicate that excitation of IC terminals in NAc via CNO was sufficient to increase exploration with PN30, but not PN50 conspecifics.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe involvement of NAc in social affective behavior is consistent with evidence implicating NAc in myriad social processes.
“The involvement of NAc in social affective behavior is consistent with evidence implicating NAc in myriad social processes.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThree rats were removed from analysis because of undetectable virus expression, or failure to show novelty preference under vehicle conditions.
“Three rats were removed from analysis because of undetect-able virus expression, or failure to show novelty preference under vehicle conditions; virus expression for the included rats is shown in Figure 6D.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNAc is a common node of the social decision-making network which integrates dopaminergic reward circuitry with neuroendocrine centers known to mediate social behavior.
“O'Connell and Hofmann (2011) placed the NAc as a common node of the social decision-making network which integrates the dopaminergic reward circuitry with the neuroendocrine centers known to mediate social behavior.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites O'Connell and Hofmann (2011)
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationNAc appears to decipher aversive from appetitive stimuli and modulate activity patterns in other social decision-making structures based on the valence of sensory information.
“Importantly, NAc appears to decipher aversive from appetitive stimuli (Xiu et al., 2014) and modulate activity patterns in other social decision-making structures based on the valence of sensory information (Johnson et al., 2017).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Xiu et al., 2014
Not checked in the free run.
- cites Johnson et al., 2017
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationRecent reports show excitation of IC projections to central amygdala promote relapse of methamphetamine use and IC projections to bed nucleus of the stria terminalis mediate negative affect during alcohol abstinence.
“Recent reports in drug administration models show excitation of IC projections to central amygdala promote relapse of methamphetamine use (Venniro et al., 2017) and IC projections to the bed nucleus of the stria terminalis mediate negative affect during alcohol abstinence (Centanni et al., 2019).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Venniro et al., 2017
Not checked in the free run.
- cites Centanni et al., 2019
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIC is a site of multisensory integration and is reciprocally connected to the extended amygdala, which may underlie its known role in human emotional recognition.
“IC is a site of multisensory integration (Rodgers et al., 2008;Gogolla et al., 2014;Gogolla, 2017) and is reciprocally connected to the extended amygdala (Shi and Cassell, 1998), which may underlie its known role in human emotional recognition (Adolphs et al., 2003;Gu et al., 2013;Terasawa et al., 2015).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Rodgers et al., 2008
Not checked in the free run.
- cites Gogolla et al., 2014
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- cites Gogolla, 2017
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May combine two claims.
InterpretationcitationAlthough we cannot be sure that approach to stressed juveniles is a prosocial response, increased NAc activity is associated with many prosocial behaviors.
“Although we cannot be sure that approach to stressed juveniles is a prosocial response, increased NAc activity is associated with many prosocial behaviors.”
Quote in the paperNot a substantial claim- Rests on an assumption: Approach to stressed juveniles is a prosocial response.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationRats require parental support to develop and survive, and the same mechanisms that evolved to enable parental care may also underlie more complex social abilities.
“Rats require parental support to develop and survive (Lamers et al., 1986), and the same mechanisms that evolved to enable parental care may also underlie more complex social abilities (Scheiber et al., 2017;Marsh, 2019).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Lamers et al., 1986
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- cites Scheiber et al., 2017
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- cites Marsh, 2019
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Classified as probably not a substantial claim.
PremisecitationThere is now substantial evidence that IC encodes and distributes negative affective states to subcortical networks to modulate behavior.
“There is now substantial evidence that IC encodes and distributes negative affective states to to subcortical networks to modulate behavior (Berret et al., 2019;Gehrlach et al., 2019).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Berret et al., 2019
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- cites Gehrlach et al., 2019
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn the SAP test, there are changes to several overt conspecific behaviors and to the pattern of ultrasonic vocalizations, which together could convey important features of conspecific stress and age.
“in the SAP test, we reported that there are changes to several overt conspecific behaviors (e.g., selfgrooming) and to the pattern of ultrasonic vocalizations, which together could convey important features of conspecific stress and age (Rogers-Carter et al., 2018b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Rogers-Carter et al., 2018b
Not checked in the free run.
May combine two claims.
Interpretationown dataOur findings that chemogenetic manipulation of IC terminals in NAc relates to adult-to-juvenile behaviors adds to these NAc-dependent prosocial behaviors and suggest an anatomical tract for socioemotional information to be integrated in social decision-making.
“Our findings that chemogenetic manipulation of IC terminals in NAc relates to adult-tojuvenile behaviors adds to these NAc-dependent prosocial behaviors and suggest an anatomical tract for socioemotional information to be integrated in social decision-making.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationOptogenetic excitation of ventral tegmental neurons that project to NAc promoted mating behavior and microinfusion of a dopamine reuptake inhibitor increased social play in rats.
“Optogenetic excitation of ventral tegmental neurons that project to the nucleus accumbens promoted mating behavior (Beny-Shefer et al., 2017) and microinfusion of a dopamine reuptake inhibitor increased social play in rats (Manduca et al., 2016).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Beny-Shefer et al., 2017
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- cites Manduca et al., 2016
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Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.
InterpretationcitationBecause these social actions are necessary for species survival, they are likely reinforced by the reward system to promote their occurrence.
“Because these social actions are necessary for species survival, they are likely reinforced by the reward system to promote their occurrence (O'Connell and Hofmann, 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites O'Connell and Hofmann, 2011
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationOxytocin in NAc increases social approach and is important for forming pair bonds.
“Similarly, oxytocin in NAc increases social approach (Steinman et al., 2019) and is important for forming pair bonds (Insel and Shapiro, 1992;Walum et al., 2012;Walum and Young, 2018).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Steinman et al., 2019
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- cites Insel and Shapiro, 1992
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- cites Walum et al., 2012
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May combine two claims.
Interpretationown dataUsing both inhibitory and excitatory tract-specific chemogenetic manipulations of IC→NAc terminals, this tract is both necessary for the preference for the stressed juvenile and sufficient to increase overall social exploration directed toward juvenile conspecifics.
“Further, using both inhibitory and excitatory tract-specific chemogenetic manipulations of IC ¡ NAc terminals, we find that this tract is both necessary for the preference for the stressed juvenile and sufficient to increase overall social exploration directed toward juvenile conspecifics.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationSilencing of IC projection to NAc decreased alcohol self-administration and increased sensitivity to alcohol, and IC projections to central amygdala drive avoidance of an aversive tastant and fear.
“Similarly, silencing of the IC projection to NAc decreased alcohol self-administration (Jaramillo et al., 2018b) and increased sensitivity to alcohol (Jaramillo et al., 2018a), and IC projections to the central amygdala drive avoidance of an aversive tastant (Schiff et al., 2018) and fear (Berret et al., 2019;Gehrlach et al., 2019).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Jaramillo et al., 2018b
Not checked in the free run.
- cites Jaramillo et al., 2018a
Not checked in the free run.
- cites Schiff et al., 2018
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationcitationAn emergent theme is that IC mediates both appetitive and aversive behavioral responses to external stimuli via different projections.
“Although more work will add clarification, an emergent theme is that IC mediates both appetitive and aversive behavioral responses to external stimuli via different projections.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIC contributes to both social approach and avoidance, the latter of which may be mediated by IC projections to central amygdala, which is necessary for social avoidance of stressed conspecifics.
“IC contributes to both social approach and avoidance (Rogers-Carter et al., 2018b), the latter of which may be mediated IC projections to the central amygdala, which is necessary for social avoidance of stressed conspecifics (Ferretti et al., 2019).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Rogers-Carter et al., 2018b
Not checked in the free run.
- cites Ferretti et al., 2019
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductown dataBilateral cannula tip placements in NAc were confirmed for experimental rats tested with PN30 (n=9) and PN50 (n=7) conspecifics.
“Map of bilateral cannula tip placements in NAc from experimental rats tested with PN30 (green; n ϭ 9) and PN50 (blue; n ϭ 7) conspecifics.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn an appetitive consummatory task, optogenetic stimulation of IC to NAc projections reduced consumption.
“Interestingly, in an appetitive consummatory task (sucrose preference) optogenetic stimulation of IC to NAc projections reduced consumption (Gehrlach et al., 2019).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gehrlach et al., 2019
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationcitationThese results parallel several features of human social behavior, namely that social stress cues modulate rodent social interactions in ways that mirror adult preference to lend help to juveniles while showing less empathy toward other adults.
“These results parallel several features of human social behavior, namely that social stress cues modulate rodent social interactions in ways that mirror adult preference to lend help to juveniles while showing less empathy toward other adults (Batson and Powell, 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Batson and Powell, 2003
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenTreatment order on days 3 and 4 was counterbalanced.
“treatment order on days 3 and 4 was counterbalanced.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataCannula tip placements in NAc were summarized.
“Summary map of cannula tip placements in NAc.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataBilateral IC sham pAAV5-hSyn-mCherry expression was confirmed in control rats (n=8).
“Map of bilateral IC sham pAAV5-hSyn-mCherry expression, n ϭ 8.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown datamCherry expression in IC was summarized for n=10.
“Summary of mCherry expression in IC (n ϭ 10)”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown datahM4D(Gi) expression spread in the IC was summarized.
“Summary of mCherry expression indicating spread of hM4D(Gi) in the IC.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataCannula tip placements in NAc were mapped.
“Map of cannula tip placements in NAc (left)”
Quote in the paperNot a substantial claim
The paper relies on this without support.
No prior mechanistic studies have explored the role of IC projection tracts in social behavior.
“No prior mechanistic studies have explored the role of IC projection tracts in social behavior.”
The paper relies on this without support.
Approach to stressed juveniles is a prosocial response.
“Although we cannot be sure that approach to stressed juveniles is a prosocial response, increased NAc activity is associated with many prosocial behaviors.”
The paper relies on this without support.
The social novelty preference test measures social reward per se.
“To establish whether IC is involved in situations of social reward per se, we used the social novelty preference test in which others have shown that an experimental rat will spend more time exploring an unfamiliar conspecific than a familiar animal and is dependent upon the NAc (Smith et al., 2018).”
The paper relies on this without support.
The conspecifics designated as stressed were indeed stressed.
“Experimental rats presented stressed PN30 conspecifics engaged in more social exploration than rats presented naive PN30 conspecifics ( p ϭ 0.008).”
The paper relies on this without support.
Fos immunoreactivity reflects neuronal activity.
“Exposure to stressed PN30 conspecifics elicited greater Fos immunoreactivity in IC ¡ NAc neurons than exposure to naive PN30 conspecifics.”
The paper relies on this without support.
CTb488 retrogradely labels NAc-projecting IC neurons.
“Schematic depicting unilateral 300 nl injections of the retrograde tracer CTb 488 in the right hemisphere NAc”
The paper relies on this without support.
TTX infusion in NAc inactivates NAc neurons without affecting adjacent regions.
“which was abolished via bilateral infusion ofTTX (100 nM, 0.5 l/side) in NAc 15 min before testing ( p ϭ 0.203).”
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?
Oxytocin signaling in insular cortex, central amygdala, and anterior cingulate cortex modulates emotion detection and responses to social affect of conspecifics.
“Additionally, oxytocin signaling in insular cortex, central amygdala, and anterior cingulate cortex modulates emotion detection and responses to social affect of conspecifics [26–28].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [26]
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.
TTX concentration differs across the paper
MajorThe methods give the TTX concentration as 10 M, whereas the Figure 1 legend says 100 nM for the same NAc infusion. The abstract gives a third concentration, 1 M, leaving the administered dose unclear.
“TTX (Tocris Bioscience) was dissolved in sterile 0.9% saline to a concentration of 10 M.”
“via bilateral infusion ofTTX (100 nM, 0.5 l/side) in NAc 15 min before testing”
Terminal-inhibition CNO pretreatment times disagree
MajorFor the PN30 IC-terminal inhibition experiment, the Results say CNO was administered 15 minutes before testing, while the Figure 4 legend says 45 minutes.
“3 weeks after testing, experimental rats underwent the SAP procedure with PN30 conspecifics after microinjections of vehicle or CNO in NAc 15 min before testing”
“which was abolished via 1 M CNO injections 45 min before testing through the guide cannula.”
A p = 0.053 result is described as a main effect
MinorThe electrophysiology Results say the ANOVA revealed a main effect at p = 0.053, although the paper specifies p < 0.05 as its significance threshold.
“A one-way repeated-measures ANOVA revealed a main effect of CNO (F (2,8) ϭ 4.33, p ϭ 0.053, h 2 ϭ 0.52)”
“Significant main effects and interactions were followed with Sidak post hoc comparisons to control experimentwise type 1 errors to p Ͻ 0.05.”
Retrograde tracer injection changes hemispheres
MinorThe methods and Figure 2 describe a right-hemisphere NAc injection, but the Results say the injections were in the left hemisphere.
“For retrograde tracing, 300 nl of cholera toxin B conjugated to Alexa Fluor 488 (CTb 488 ; Thermo Fisher, catalog #C34775) were microinjected to the right hemisphere NAc”
“12 experimental rats received unilateral microinjections of the retrograde tracer CTb 488 in the left hemisphere NAc”
Terminal-activation CNO pretreatment times disagree
MinorFor the IC-terminal activation experiment, the Results place CNO infusion 30 minutes before testing, but the Figure 5 legend places it 45 minutes before testing.
“the other after infusion of CNO (0.5 l/side) to NAc 30 min before testing”
“Terminal excitation of mCherry-positive fibers was achieved via bilateral CNO microinjections to NAc (1 M) 45 min before testing.”
Adult preference-score t test has the wrong degrees of freedom
MinorFigure 4 reports nine rats for the PN50 experiment. A paired t test of their vehicle and CNO preference scores would have eight, not nine, degrees of freedom; the preceding ANOVA also uses an error degree of freedom of eight.
Reported 9 · recomputed 8
“Converting these results to percentage preference scores revealed no effect of CNO (t (9) ϭ 0.57, p ϭ 0.293).”
PN50 TTX preference-score p values disagree
MinorThe Results and the Figure 1 legend give different p values for the effect of TTX on PN50 preference scores.
“TTX did not alter preference scores in experimental rats tested with PN50 conspecifics ( p ϭ 0.651).”
“Rats tested with PN50 conspecifics show a preference for naive conspecifics, which was unaffected by TTX treatment ( p ϭ 0.452).”
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“IC to NAcc circuits have been regarded as the key brain region that regulates social approach behaviors to the stressed juvenile in rats (Rogers-Carter et al., 2019).”
BackgroundTranslational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry
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- Authors
- Rogers-Carter, M. M., Djerdjaj, A., Gribbons, K. B., Varela, J. A., & Christianson, J. P.
- Affiliations
- Boston College (US)
- Corresponding author
- Rogers-Carter, Morgan M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2019-10-07
- Volume
- 39
- Issue
- 44
- Pages
- 8717-8729
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6820210
- OpenAlex
- W2977766168
- Semantic Scholar
- 4c0c4d79dad7e32adb8154c16b52662bbb81f6c7
- Cited by
- 79
- References
- 82
- Citations by year
- 2026: 15 · 2025: 9 · 2024: 7 · 2023: 14 · 2022: 11 · 2021: 13 · 2020: 7 · 2019: 3
- FWCI
- 10.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Boston College
- National Institutes of Health
- National Institute of Mental Health (R56MH109545, R01MH119422)
- 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 › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- insula, nucleus accumbens core, social approach, social decision-making, juvenile stress, tetrodotoxin, Fos-like immunoreactivity, chemogenetic manipulation, social reward, autism spectrum disorder
- MeSH terms
- Animals, Cerebral Cortex, Choice Behavior, Male, Neural Pathways, Nucleus Accumbens, Social Behavior, Stress, Psychological, Rats, Sprague-Dawley
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