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Cited by 72Neuroendocrine regulation and behaviorNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Neural circuits regulating prosocial behaviors

Open access
Walsh, Jessica J., Christoffel, Daniel J., Malenka, Robert C.·2023·Neuropsychopharmacology
DOI 10.1038/s41386-022-01348-8PMC PMC9700801
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Abstract

Positive, prosocial interactions are essential for survival, development, and well-being. These intricate and complex behaviors are mediated by an amalgamation of neural circuit mechanisms working in concert. Impairments in prosocial behaviors, which occur in a large number of neuropsychiatric disorders, result from disruption of the coordinated activity of these neural circuits. In this review, we focus our discussion on recent findings that utilize modern approaches in rodents to map, monitor, and manipulate neural circuits implicated in a variety of prosocial behaviors. We highlight how modulation by oxytocin, serotonin, and dopamine of excitatory and inhibitory synaptic transmission in specific brain regions is critical for regulation of adaptive prosocial interactions. We then describe how recent findings have helped elucidate pathophysiological mechanisms underlying the social deficits that accompany neuropsychiatric disorders. We conclude by discussing approaches for the development of more efficacious and targeted therapeutic interventions to ameliorate aberrant prosocial behaviors.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes rodent circuit studies showing that prosocial behaviors are regulated by coordinated oxytocin, serotonin, and dopamine actions across mesolimbic and related circuits, especially the nucleus accumbens, ventral tegmental area, dorsal raphe, medial prefrontal cortex, amygdala, septum, and hippocampus. It links disruption of these circuits to social deficits in autism spectrum disorder, schizophrenia, substance use disorder, and stress-related disorders, and discusses therapeutic directions.

Key findings

  • Oxytocin in the nucleus accumbens (NAc) promotes social reward by inducing serotonin release from dorsal raphe inputs acting on presynaptic 5-HT1b receptors; optogenetic activation of dorsal raphe 5-HT inputs in NAc increases sociability, inhibition decreases it, and 5-HT1b blockade prevents the enhanced sociability.
  • MDMA’s prosocial effects in mice require 5-HT release and SERT/5-HT1b receptors in NAc, not the dopamine transporter; methamphetamine did not enhance sociability. VTA dopamine activity increases during social operant lever pressing, and optogenetic inhibition of VTA dopamine neurons impairs social reinforcement learning.
  • Social memory depends on hippocampal CA2 and a medial septum-to-CA2 circuit: medial septum 5-HT1b receptor activity and median raphe 5-HT inputs bidirectionally influence social memory, while oxytocin and vasopressin modulation of CA2 is also required. Empathy-related behaviors involve ACC-to-NAc projections for social transfer of pain and ACC/insula-to-BLA projections for social transfer of fear, with oxytocin modulation.
  • In ASD models, 16p11.2 deletion in dorsal raphe 5-HT neurons causes sociability deficits rescued by optogenetic activation of dorsal raphe 5-HT inputs to NAc; a 5-HT1b agonist rescued sociability deficits in six different mouse models for ASD, and MDMA ameliorated sociability deficits in four different ASD mouse models. In schizophrenia models, 22q11.2 deletion social memory deficits are linked to CA2 parvalbumin interneurons and TREK-1, while 16p11.2 duplication alters hippocampal-orbitofrontal-amygdala connectivity.

Methods

  • Design: narrative review of recent rodent studies using circuit mapping, monitoring, and manipulation approaches, including optogenetics, chemogenetics, fiber photometry, slice electrophysiology, transgenic driver lines, and behavioral assays.
  • Data/sample: published findings primarily in mice, with some prairie vole studies; no new experimental data are reported.
  • Main analysis: qualitative synthesis of circuit mechanisms for sociability, social reward, social memory, and empathy-related behaviors, plus discussion of neuropsychiatric models and therapeutic strategies.

Limitations

  • The paper states assay-specific limitations: juvenile interaction behavior can be highly variable and occasionally aggressive; three-chamber social approach may be confounded by aggression, sexual motivation, prior stress, illness, or previous aggression; social CPP requires control assays to rule out memory deficits; machine-learning behavioral tools have equipment requirements and identity-swapping problems, with manual scoring by expert behaviorists remaining the gold standard.
  • The paper notes that earlier in vitro slice studies stimulated unknown excitatory inputs, that input-specific filtering of NAc excitatory inputs by 5-HT and dopamine does not yet provide a clear answer for prosocial behavior, and that sex-specific effects and species differences—such as oxytocin receptor-expressing neurons in ACC of prairie voles but not mice—require attention.
  • Evident from the text: this is not a systematic review or meta-analysis, it focuses on non-sexual, non-aggressive prosocial behaviors in rodents, and many circuit mechanisms remain unresolved or require substantially more work.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41386-022-01348-8

Cites

191 of 191 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 201 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    The prosocial effect of systemic MDMA on sociability was mimicked by direct infusion of MDMA into the nucleus accumbens.

    “In mice, systemic administration of a prosocial dose of MDMA enhanced sociability in the three-chamber assay, an effect that was mimicked by direct infusion of MDMA into the NAc, prevented by pharmacological inhibition of the 5-HT transporter (SERT) or its genetic deletion, and blocked by direct infusion into the NAc of a 5-HT1b receptor antagonist [51].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] Heifets BD, Salgado JS, Taylor MD, Hoerbelt P, Cardozo Pinto DF, Steinberg EE, et al. Distinct neural mechanisms for the prosocial and rewarding properties of MDMA. Sci Transl Med. 2019;11:1–11. source

      Not checked in the free run.

  • Premisecitation

    The prosocial effect of systemic MDMA on sociability was blocked by direct infusion into the nucleus accumbens of a 5-HT1b receptor antagonist.

    “In mice, systemic administration of a prosocial dose of MDMA enhanced sociability in the three-chamber assay, an effect that was mimicked by direct infusion of MDMA into the NAc, prevented by pharmacological inhibition of the 5-HT transporter (SERT) or its genetic deletion, and blocked by direct infusion into the NAc of a 5-HT1b receptor antagonist [51].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] Heifets BD, Salgado JS, Taylor MD, Hoerbelt P, Cardozo Pinto DF, Steinberg EE, et al. Distinct neural mechanisms for the prosocial and rewarding properties of MDMA. Sci Transl Med. 2019;11:1–11. source

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  • Premisecitation

    A major advance in understanding mammalian prosocial behaviors came from seminal studies investigating the role of oxytocin in voles.

    “A major advance in the current understanding of mammalian prosocial behaviors came from seminal studies that investigated the role of oxytocin (OXT) in voles, a neuropeptide that is well established to play critical roles in social and affiliative behaviors [9,10].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Froemke RC, Young LJ. Oxytocin, neural plasticity, and social behavior. Annu Rev Neurosci. 2021;44:359–81. source

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    • cites [10] Young LJ, Lim MM, Gingrich B, Insel TR. Cellular mechanisms of social attachment. Horm Behav. 2001;40:133–8. source

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  • Interpretationnone given

    Modulation by oxytocin, serotonin, and dopamine of excitatory and inhibitory synaptic transmission in specific brain regions is critical for regulation of adaptive prosocial interactions.

    “We highlight how modulation by oxytocin, serotonin, and dopamine of excitatory and inhibitory synaptic transmission in specific brain regions is critical for regulation of adaptive prosocial interactions.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Modifications in the conditioned place preference assay have expanded its use to investigate the rewarding properties of prosocial interactions.

    “More recently, modifications in the CPP assay have been made to expand its use to investigate the rewarding properties of prosocial interactions [40,41].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [40] Panksepp JB, Lahvis GP. Social reward among juvenile mice. Genes Brain Behav. 2007;6:661–71. source

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    • cites [41] Dolen G, Darvishzadeh A, Huang KW, Malenka RC. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature. 2013;501:179–84. source

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  • Classified as probably not a substantial claim. 15
  • May combine two claims. 49

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

    Premisecitation

    Serotonin release in the central nervous system has been implicated in regulating a broad range of behaviors, including sociability.

    “For decades, 5-HT release in the central nervous system has been implicated in regulating a broad range of behaviors, including sociability [3,18,[44][45][46].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Charney DS, Sklar PB, Buxbaum JD, Nestler EJ. Charney & Nestler’s neurobiology of mental illness. 5th ed. New York: Oxford University Press; 2018. source

      Not checked in the free run.

    • cites [18] Brown S-L, Praag HMv. The role of serotonin in psychiatric disorders. New York: Brunner/Mazel; 1991.

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    • cites [44] Kiser D, Steemers B, Branchi I, Homberg JR. The reciprocal interaction between serotonin and social behaviour. Neurosci Biobehav Rev. 2012;36:786–98. source

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    Premisecitation

    There is a critical developmental window during adolescence when mice can optimally learn social rewarding cues and thereby exhibit social conditioned place preference.

    “It has also been reported that there is a critical developmental window during adolescence when mice can optimally learn social rewarding cues and thereby exhibit social CPP [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Nardou R, Lewis EM, Rothhaas R, Xu R, Yang A, Boyden E, et al. Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature. 2019;569:116–20. source

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    Premisecitation

    Many variables may influence social approach behavior, such as prior stress, illness, or previous aggressive behavior within a home cage.

    “In addition, there are many variables that may influence social approach behavior, such as prior stress, illness, or previous aggressive behavior within a home cage [38].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Yang M, Silverman JL, Crawley JN. Automated three-chambered social approach task for mice. Curr Protoc Neurosci. 2011;56:8.26.1–8.26.16. source

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    Premisecitation

    Optogenetic activation of dorsal raphe serotonin inputs in the nucleus accumbens increased sociability while optogenetic inhibition decreased sociability, as measured by juvenile interaction and three-chamber sociability assays.

    “Work utilizing a circuit-based approach to examine the role of 5-HT release from DR inputs in the NAc revealed that optogenetic activation of DR 5-HT inputs increased sociability while optogenetic inhibition of these inputs decreased sociability, as measured by the juvenile interaction and three-chamber sociability assays [47].”
    • Also stated in: § NEURAL MECHANISMS OF PROSOCIAL BEHAVIOR AND SOCIAL REWARD · plain
      “Thus, modulations of DR 5-HT input activity in the NAc bidirectionally influenced sociability.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Walsh JJ, Christoffel DJ, Heifets BD, Ben-Dor GA, Selimbeyoglu A, Hung LW, et al. 5-HT release in nucleus accumbens rescues social deficits in mouse autism model. Nature. 2018;560:589–94. source

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  • May combine two claims.

    Premisecitation

    Oxytocin induces serotonin release from dorsal raphe inputs in the nucleus accumbens, which acts on presynaptic 5-HT1b receptors that are also required for social reward.

    “Additional experimental manipulations suggested that OXT induces 5-HT release from dorsal raphe (DR) inputs in the NAc, which acts on presynaptic 5-HT1b receptors that are also required for social reward [41].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Dolen G, Darvishzadeh A, Huang KW, Malenka RC. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature. 2013;501:179–84. source

      Not checked in the free run.

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    Premisecitation

    MDMA has powerful prosocial effects in humans and is a potent releaser of monoamines, which preferentially increases serotonin release.

    “Further support for the notion that 5-HT release in the NAc promotes sociability came from the study of the mechanism of action of (±) 3,4-methylenedioxymetham-phetamine (MDMA), the Schedule 1 recreational drug, which has powerful prosocial effects in humans and is a potent releaser of monoamines, which preferentially increases 5-HT release [48][49][50].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48][49][50]

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    Premisecitation

    Social conditioned place preference assays have traditionally been used to investigate the rewarding properties of stimuli such as drugs of abuse and natural rewards.

    “CPP assays have traditionally been used to investigate the rewarding properties of stimuli, such as drugs of abuse and natural rewards [39].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Tzschentke TM. Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol. 2007;12:227–462. source

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    Premisecitation

    Sex-specific differences in the effects of activating oxytocin receptor positive medial prefrontal cortex interneurons have been reported, with activation inducing anxiety in males but promoting social behavior in females.

    “For example, sex-specific differences in the effects of activating OXT receptor positive mPFC interneurons have been reported with activation inducing anxiety in males, but promoting social behavior in females [68,69].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [68] Nakajima M, Gorlich A, Heintz N. Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons. Cell. 2014;159:295–305. source

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    • cites [69] Li K, Nakajima M, Ibanez-Tallon I, Heintz N. A cortical circuit for sexually dimorphic oxytocin-dependent anxiety behaviors. Cell. 2016;167:60–72.e11. source

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    Premisecitation

    Excitotoxic lesions of CA2 blocked the formation of a social memory but not an olfactory memory.

    “Excitotoxic lesions of CA2 also blocked the formation of a social memory but not an olfactory memory [84].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [84] Stevenson EL, Caldwell HK. Lesions to the CA2 region of the hippocampus impair social memory in mice. Eur J Neurosci. 2014;40:3294–301. source

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    Premisecitation

    Bath application of dopamine or methamphetamine depressed responses generated by paraventricular thalamus inputs while having minimal effects on those generated by ventral hippocampus, basolateral amygdala, and medial prefrontal cortex inputs.

    “In marked contrast, bath application of DA or methamphetamine (to release endogenous DA) depressed responses generated by PVT inputs while having minimal effects on those generated by the three other brain regions.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] Christoffel DJ, Walsh JJ, Hoerbelt P, Heifets BD, Llorach P, Lopez RC, et al. Selective filtering of excitatory inputs to nucleus accumbens by dopamine and serotonin. Proc Natl Acad Sci USA. 2021;118:1–10. source

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    Premisecitation

    Optogenetic inhibition of basolateral amygdala-to-nucleus accumbens inputs enhanced sociability in wild-type mice and reversed social deficits in Shank3-/- mice, while activation of these inputs reduced sociability in wild-type mice.

    “Optogenetic inhibition of BLA-to-NAc inputs was found to enhance sociability in wild-type mice and reverse social deficits in Shank3 -/-mice while activation of these inputs reduced sociability in wild-type mice [66].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] Folkes OM, Baldi R, Kondev V, Marcus DJ, Hartley ND, Turner BD, et al. An endocannabinoid-regulated basolateral amygdala-nucleus accumbens circuit modulates sociability. J Clin Invest. 2020;130:1728–42. source

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    Premisecitation

    CA2 pyramidal cell activity remapped during social interactions, but unlike CA1 pyramidal cell activity, did not remap to changes in spatial cues.

    “Furthermore, CA2 pyramidal cell activity remapped during social interactions, but unlike CA1 pyramidal cell activity, did not remap to changes in spatial cues [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Alexander GM, Farris S, Pirone JR, Zheng C, Colgin LL, Dudek SM. Social and novel contexts modify hippocampal CA2 representations of space. Nat Commun. 2016;7:10300. source

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    Premisecitation

    Inhibition of either paraventricular thalamus-to-nucleus accumbens or medial prefrontal cortex-to-nucleus accumbens inputs did not alter sociability, although the latter manipulation prevented the enhanced sociability elicited by systemic MDMA administration.

    “In contrast, inhibition of either PVTto-NAc or mPFC-to-NAc inputs did not alter sociability although the latter manipulation prevented the enhanced sociability elicited by systemic MDMA administration [65].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] Christoffel DJ, Walsh JJ, Hoerbelt P, Heifets BD, Llorach P, Lopez RC, et al. Selective filtering of excitatory inputs to nucleus accumbens by dopamine and serotonin. Proc Natl Acad Sci USA. 2021;118:1–10. source

      Not checked in the free run.

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    Premisecitation

    Chemogenetic inhibition of medial septum neurons projecting to CA2 impaired social memory while having no effects on basal sociability or inanimate object memory.

    “Chemogenetic inhibition of MS neurons projecting to CA2 impaired social memory while having no effects on basal sociability or inanimate object memory.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] Wu X, Morishita W, Beier KT, Heifets BD, Malenka RC. 5-HT modulation of a medial septal circuit tunes social memory stability. Nature. 2021;599:96–101. source

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  • May combine two claims.

    Premisecitation

    Oxytocin receptor activation induces burst firing of CA2 pyramidal neurons and conditional deletion of these receptors abolishes social memory.

    “Similarly, OXT receptor activation induces burst firing of CA2 pyramidal neurons and conditional deletion of these receptors abolishes social memory [77][78][79].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [77][78][79]

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    Premisecitation

    VTA dopamine activity increased during lever pressing in a social instrumental operant task and optogenetic inhibition of VTA dopamine neurons impaired social reinforcement learning.

    “Consistent with an involvement of DA in the reinforcing properties of a social interaction, VTA DA activity increased during lever pressing in a social instrumental operant task and optogenetic inhibition of VTA DA neurons impaired social reinforcement learning [57].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] Solie C, Girard B, Righetti B, Tapparel M, Bellone C. VTA dopamine neuron activity encodes social interaction and promotes reinforcement learning through social prediction error. Nat Neurosci. 2022;25:86–97. source

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    Premisecitation

    Inhibition of basolateral amygdala-to-nucleus accumbens inputs enhanced sociability, but inhibition of ventral hippocampus-to-nucleus accumbens inputs decreased sociability.

    “Consistent with these findings, we found that inhibition of BLA-to-NAc inputs enhanced sociability but surprisingly observed a decrease in sociability when vHip-to-NAc inputs were optogenetically inhibited [65].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] Christoffel DJ, Walsh JJ, Hoerbelt P, Heifets BD, Llorach P, Lopez RC, et al. Selective filtering of excitatory inputs to nucleus accumbens by dopamine and serotonin. Proc Natl Acad Sci USA. 2021;118:1–10. source

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  • May combine two claims.

    Interpretationreasoning

    Serotonin release, but not dopamine release, in the nucleus accumbens is required for the prosocial effects of MDMA.

    “Together, these findings suggest that 5-HT release, but not DA release, in the NAc is required for the prosocial effects of MDMA.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Oxytocin contributes to promoting sociability and social reward not only by enhancing serotonin release in the nucleus accumbens, but also by increasing excitatory drive on VTA dopamine neurons that project to the nucleus accumbens.

    “Furthermore, several lines of evidence suggest that OXT contributes to promoting sociability and social reward not only by enhancing 5-HT release in the NAc, but also by increasing excitatory drive on VTA DA neurons that project to NAc [59][60][61].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59][60][61]

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    Premisecitation

    Modulation of CA2 parvalbumin-positive interneurons is critical for social memory in that they exhibit a heterosynaptic form of input-timing-dependent inhibitory long-term depression, the blockade of which impairs social memory.

    “Modulation of CA2 parvalbumin-positive (PV) interneurons is also critical for social memory in that they exhibit a heterosynaptic form of inputtiming-dependent inhibitory LTD, the blockade of which impairs social memory [75,76].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [75] Leroy F, Brann DH, Meira T, Siegelbaum SA. Input-timing-dependent plasticity in the hippocampal CA2 region and its potential role in social memory. Neuron. 2017;95:1089–102.e5. source

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    • cites [76] Dominguez S, Rey CC, Therreau L, Fanton A, Massotte D, Verret L, et al. Maturation of PNN and ErbB4 signaling in area CA2 during adolescence underlies the emergence of PV interneuron plasticity and social memory. Cell Rep. 2019;29:1099–112.e4. source

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

    Premisecitation

    Optogenetic activation of nucleus accumbens-projecting dopamine neurons can influence prosocial behaviors.

    “This is a surprising result, which deserves further exploration, given that optogenetic activation of NAc-projecting DA neurons can influence prosocial behaviors [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Gunaydin LA, Grosenick L, Finkelstein JC, Kauvar IV, Fenno LE, Adhikari A, et al. Natural neural projection dynamics underlying social behavior. Cell. 2014;157:1535–51. source

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  • May combine two claims.

    Interpretationown data

    Social memory is regulated by a complex neural network involving serotonin regulation of a medial septum-to-CA2 circuit with further direct modulation of dorsal CA2 by oxytocin and vasopressin.

    “This body of work begins to elucidate components of a complex neural network regulating social memory involving 5-HT regulation of a MS-to-CA2 circuit with further direct modulation of dorsal CA2 by OXT and Avp.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Inhibition of anterior cingulate cortex-to-nucleus accumbens core projections did not influence the social transfer of fear, which was reduced by inhibition of anterior cingulate cortex-to-basolateral amygdala projections.

    “Surprisingly this same manipulation did not influence the social transfer of fear, which was reduced by inhibition of ACC-to-BLA projections, as previously demonstrated [102].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] Allsop SA, Wichmann R, Mills F, Burgos-Robles A, Chang CJ, Felix-Ortiz AC, et al. Corticoamygdala transfer of socially derived information gates observational learning. Cell. 2018;173:1329–42.e18. source

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    Premisecitation

    Social transfer of fear is routinely assayed as increased freezing by an observer and can occur via direct observation of a demonstrator being shocked or indirectly via interaction with a conditioned subject responding to a cue.

    “Social transfer of fear, routinely assayed as increased freezing by an observer, is a particularly robust form of emotional contagion and can occur via direct observation of a demonstrator being shocked or indirectly via interaction with a conditioned subject responding to a cue [103-105].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [103] Jeon D, Kim S, Chetana M, Jo D, Ruley HE, Lin SY, et al. Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC. Nat Neurosci. 2010;13:482–8. source

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    • cites [104] Morozov A. Behavioral modulation by social experiences in rodent models. Curr Protoc Neurosci. 2018;84:e50. source

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    • cites [105] Debiec J, Olsson A. Social fear learning: from animal models to human function. Trends Cogn Sci. 2017;21:546–55. source

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    Premisecitation

    Multiple sensory modalities are implicated in mediating the social transfer of pain, with both the assay and species under investigation critically determining the dominant modality.

    “Multiple sensory modalities are implicated in mediating the social transfer of pain, with both the assay and species under investigation critically determining the dominant modality [88,89].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [88] Panksepp JB, Lahvis GP. Rodent empathy and affective neuroscience. Neurosci Biobehav Rev. 2011;35:1864–75. source

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    • cites [89] Smith ML, Hostetler CM, Heinricher MM, Ryabinin AE. Social transfer of pain in mice. Sci Adv. 2016;2:e1600855. source

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  • May combine two claims.

    Interpretationcitation

    Processing of social information by dorsal CA2, possibly in the form of sharp-wave ripples, is relayed to ventral CA1 that in turn influences downstream limbic structures including the nucleus accumbens and medial prefrontal cortex.

    “This processing of social information by dorsal CA2, possibly in the form of sharp-wave ripples [86], is then relayed to ventral CA1 that in turn influences downstream limbic structures including the NAc and mPFC.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] Oliva A, Fernandez-Ruiz A, Leroy F, Siegelbaum SA. Hippocampal CA2 sharp-wave ripples reactivate and promote social memory. Nature. 2020;587:264–69. source

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    Premisecitation

    Local infusion of specific receptor antagonists into the medial septum revealed that oxytocin receptors were not required for social memory, which was prevented by a selective 5-HT1b receptor antagonist.

    “However, local infusion of specific receptor antagonists into the MS revealed that OXT receptors were not required for social memory, which was prevented by a selective 5-HT1b receptor antagonist.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] Wu X, Morishita W, Beier KT, Heifets BD, Malenka RC. 5-HT modulation of a medial septal circuit tunes social memory stability. Nature. 2021;599:96–101. source

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    Premisecitation

    Observational learning or social transfer has been observed for pain, fear, stress, food preference, consolation, and helping behavior.

    “Such observational learning or social transfer has been observed for pain, fear, stress, food preference, consolation and helping behavior [89][90][91][92][93][94].”
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    • cites [89][90][91]

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    Premisecitation

    Inhibition of insula-to-basolateral amygdala circuits alters social approach to a distressed conspecific, although the effects of this manipulation on social transfer of fear were not investigated.

    “On the other hand, inhibition of insula-to-BLA circuits alter social approach to a distressed conspecific, although the effects of this manipulation on social transfer of fear were not investigated [107].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [107] Rogers-Carter MM, Varela JA, Gribbons KB, Pierce AF, McGoey MT, Ritchey M, et al. Insular cortex mediates approach and avoidance responses to social affective stimuli. Nat Neurosci. 2018;21:404–14. source

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    Premisecitation

    The 15q11.3 duplication mouse model exhibits reduced excitatory transmission in DR 5-HT neurons and low glucose metabolism in the DR, suggesting reduced DR 5-HT activity.

    “chromosomal 15q11.3duplication, exhibits reduced excitatory transmission in DR 5-HT neurons and low glucose metabolism in the DR, suggesting reduced DR 5-HT activity [122].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [122] Nakai N, Nagano M, Saitow F, Watanabe Y, Kawamura Y, Kawamoto A, et al. Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice. Sci Adv. 2017;3:e1603001. source

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  • May combine two claims.

    Interpretationreasoning

    Social deficits present in SZ may involve impaired recognition as well as reduced motivation.

    “suggesting that social deficits present in SZ may involve impaired recognition as well as reduced motivation.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Chronic stressors cause maladaptive adaptations in the mesolimbic DA system, the details of which seem to be influenced by the nature and degree of the stressor.

    “A number of studies have found that chronic stressors cause maladaptive adaptations in the mesolimbic DA system [148], the details of which seem to be influenced by the nature and the degree of the stressor.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [148] Fox ME, Lobo MK. The molecular and cellular mechanisms of depression: a focus on reward circuitry. Mol Psychiatry. 2019;24:1798–815. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In prairie voles, repeated amphetamine exposure inhibited pair bonding, decreased OXT levels in the mPFC and increased NAc DA levels.

    “In prairie voles, repeated amphetamine exposure inhibited pair bonding, decreased OXT levels in the mPFC and increased NAc DA levels [143].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [143] Young KA, Liu Y, Gobrogge KL, Wang H, Wang Z. Oxytocin reverses amphetamine-induced deficits in social bonding: evidence for an interaction with nucleus accumbens dopamine. J Neurosci. 2014;34:8499–506. source

      Not checked in the free run.

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

    Premisecitation

    CNVs, both deletions and duplications, have been implicated in SZ.

    “CNVs, both deletions and duplications, have been implicated in SZ [132-134]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [132] Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet. 2008;40:880–5. source

      Not checked in the free run.

    • cites [133] Malhotra D, Sebat J. CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell. 2012;148:1223–41. source

      Not checked in the free run.

    • cites [134] McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, et al. 22q11.2 deletion syndrome. Nat Rev Dis Prim. 2015;1:15071. source

      Not checked in the free run.

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

    Premisecitation

    E/I imbalance in the ACC, but not the mPFC, contributes to social deficits in Shank3 deletion mice.

    “a different group found that E/I imbalance in the ACC, but not the mPFC, contribute to social deficits in Shank3 deletion mice [129].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [129] Guo B, Chen J, Chen Q, Ren K, Feng D, Mao H, et al. Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice. Nat Neurosci. 2019;22:1223–34. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cntnap2 KO mice exhibit a reduction in both excitatory and inhibitory synaptic inputs onto L2/3 pyramidal neurons and perturbed oscillatory activity in the mPFC.

    “these mice exhibit a reduction in both excitatory and inhibitory synaptic inputs onto L2/3 pyramidal neurons and perturbed oscillatory activity in the mPFC [127].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] Lazaro MT, Taxidis J, Shuman T, Bachmutsky I, Ikrar T, Santos R, et al. Reduced prefrontal synaptic connectivity and disturbed oscillatory population dynamics in the CNTNAP2 model of autism. Cell Rep. 2019;27:2567–78.e6. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In four etiologically distinct ASD mouse models, altered E/I balance was observed in the somatosensory cortex without corresponding changes in overall circuit excitability, suggesting altered E/I balance may be homeostatic compensation and not a primary mechanism mediating social impairments.

    “in four etiologically distinct ASD mouse models, altered E/I balance was observed in the somatosensory cortex, without any corresponding changes in overall circuit excitability, suggesting altered E/I balance may be homeostatic compensation and not a primary mechanism mediating social impairments [131].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [131] Antoine MW, Langberg T, Schnepel P, Feldman DE. Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models. Neuron. 2019;101:648–61.e4. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mice with 16p11.2 duplication exhibit impaired social behavior and compromised hippocampal-orbitofrontal cortex-amygdala functional connectivity.

    “Mice with 16p11.2duplication exhibit impaired social behavior, as well as compromised hippocampal-orbitofrontal cortex-amygdala functional connectivity, which was assessed using network analysis of 14C-2deoxyglucose imaging data [138].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [138] Bristow GC, Thomson DM, Openshaw RL, Mitchell EJ, Pratt JA, Dawson N, et al. 16p11 duplication disrupts hippocampal-orbitofrontal-amygdala connectivity, revealing a neural circuit endophenotype for schizophrenia. Cell Rep. 2020;31:107536. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Df(16)A+/- mice exhibited decreased firing of CA2 pyramidal neurons during the three-chamber sociability assay, perhaps due to increased current through a K+ channel (TREK-1).

    “these mice exhibited decrease firing of CA2 pyramidal neurons during the three-chamber sociability assay, perhaps due to increased current through a K+ channel (TREK-1) [73].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] Piskorowski RA, Nasrallah K, Diamantopoulou A, Mukai J, Hassan SI, Siegelbaum SA, et al. Age-dependent specific changes in area CA2 of the hippocampus and social memory deficit in a mouse model of the 22q11.2 deletion syndrome. Neuron. 2016;89:163–76. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Prosocial interactions have high appetitive valence and can exert powerful effects on decreasing pathological behaviors associated with substance use disorder.

    “These observations demonstrate the high appetitive valence of prosocial interactions and the powerful effects they can exert on decreasing pathological behaviors associated with substance use disorder.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Direct infusion of OXT into the mPFC restored pair bonding and normalized NAc DA levels in prairie voles after amphetamine exposure.

    “Direct infusion of OXT into the mPFC restored pair bonding and normalized NAc DA levels [143].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [143] Young KA, Liu Y, Gobrogge KL, Wang H, Wang Z. Oxytocin reverses amphetamine-induced deficits in social bonding: evidence for an interaction with nucleus accumbens dopamine. J Neurosci. 2014;34:8499–506. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The presence of a drug-naïve peer reduces drug seeking while the presence of an individual associated with previous drug use promotes relapse.

    “the presence of a drug-naïve peer reduces drug seeking while the presence of an individual associated with previous drug use promotes relapse [144].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [144] Bardo MT, Neisewander JL, Kelly TH. Individual differences and social influences on the neurobehavioral pharmacology of abused drugs. Pharm Rev. 2013;65:255–90. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Infusion of OXT into the mPFC following CSDS had antidepressant actions, associated with increased DA levels and enhanced excitatory synaptic transmission in the mPFC.

    “infusion of OXT into the mPFC following CSDS had antidepressant actions, which were associated with increased DA levels, as well as enhanced excitatory synaptic transmission, in the mPFC [162].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [162] Li Q, Zhang B, Cao H, Liu W, Guo F, Shen F, et al. Oxytocin exerts antidepressant-like effect by potentiating dopaminergic synaptic transmission in the mPFC. Neuropharmacology. 2020;162:107836. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CSDS increases inhibitory transmission from the ventral pallidum-to-VTA, and inhibiting this circuit restored normal social interactions.

    “CSDS also increases inhibitory transmission from the ventral pallidum-to-VTA, the importance of which was demonstrated by the finding that inhibiting this circuit restored normal social interactions [153].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [153] Knowland D, Lilascharoen V, Pacia CP, Shin S, Wang EH, Lim BK. Distinct ventral pallidal neural populations mediate separate symptoms of depression. Cell. 2017;170:284–97.e18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MDMA has well-documented prosocial effects in human subjects, and a pilot study found that MDMA-assisted psychotherapy reduced social anxiety in ASD adults.

    “MDMA has well documented prosocial effects in human subjects and a pilot study found that MDMA-assisted psychotherapy reduced social anxiety in ASD adults [178].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [178] Danforth AL, Grob CS, Struble C, Feduccia AA, Walker N, Jerome L, et al. Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology. 2018;235:3137–48. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    One week of social isolation during adolescence resulted in increased excitability of mPFC-projecting VTA DA neurons and increased social interaction but decreased social novelty preference.

    “1 week of social isolation during adolescence resulted in increased excitability of mPFC-projecting VTA DA neurons and increased social interaction but decreased social novelty preference [155].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [155] Musardo S, Contestabile A, Knoop M, Baud O, Bellone C. Oxytocin neurons mediate the effect of social isolation via the VTA circuits. Elife. 2022;11:73421–42. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Inhibition of BLA-to-mPFC or BLA-to-vHip inputs decreased anxiety while also enhancing social interactions.

    “inhibition of BLA-to-mPFC or BLA-to-vHip inputs decreased anxiety while also enhancing social interactions [167][168][169].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [167][168][169]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Alterations in VTA DA activity affect activity in multiple downstream targets, including the NAc and mPFC, which appear to be particularly important for mediating social avoidance.

    “Alterations in VTA DA activity will affect activity in multiple downstream targets, including the NAc and mPFC, which appear to be particularly important for mediating social avoidance [149, 150, 156-159].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [149] Walsh JJ, Friedman AK, Sun H, Heller EA, Ku SM, Juarez B, et al. Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway. Nat Neurosci. 2014;17:27–9. source

      Not checked in the free run.

    • cites [150] Tye KM, Mirzabekov JJ, Warden MR, Ferenczi EA, Tsai HC, Finkelstein J, et al. Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature. 2013;493:537–41. source

      Not checked in the free run.

    • cites [156] Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM, Koo JW, et al. Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature. 2013;493:532–6. source

      Not checked in the free run.

    • cites [157] Hultman R, Ulrich K, Sachs BD, Blount C, Carlson DE, Ndubuizu N, et al. Brain-wide electrical spatiotemporal dynamics encode depression vulnerability. Cell. 2018;173:166–80.e14. source

      Not checked in the free run.

    • cites [158] Koo JW, Chaudhury D, Han MH, Nestler EJ. Role of mesolimbic brain-derived neurotrophic factor in depression. Biol Psychiatry. 2019;86:738–48. source

      Not checked in the free run.

    • cites [159] Christoffel DJ, Golden SA, Russo SJ. Structural and synaptic plasticity in stress-related disorders. Rev Neurosci. 2011;22:535–49. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Peripheral levels of vasopressin appear to be an accurate predictor of ASD and was effective at ameliorating social deficits when administered intranasally in a small trial.

    “Peripheral levels of vasopressin appear to be an accurate predictor of ASD and was effective at ameliorating social deficits when administered intranasally in a small trial [175, 176].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [175] Parker KJ, Oztan O, Libove RA, Mohsin N, Karhson DS, Sumiyoshi RD, et al. A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism. Sci Transl Med. 2019;11:1–26. source

      Not checked in the free run.

    • cites [176] Oztan O, Garner JP, Constantino JN, Parker KJ. Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder. Proc Natl Acad Sci USA. 2020;117:10609–13. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Acute stress may promote social interactions at least in part via upregulation of DA input activity in the mPFC, whereas chronic stressors appear to lead to a hypodopaminergic state.

    “Thus, acute stress may promote social interactions at least in part via upregulation of DA input activity in the mPFC [155], whereas chronic stressors appear to lead to a hypodopaminergic state [162].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [155] Musardo S, Contestabile A, Knoop M, Baud O, Bellone C. Oxytocin neurons mediate the effect of social isolation via the VTA circuits. Elife. 2022;11:73421–42. source

      Not checked in the free run.

    • cites [162] Li Q, Zhang B, Cao H, Liu W, Guo F, Shen F, et al. Oxytocin exerts antidepressant-like effect by potentiating dopaminergic synaptic transmission in the mPFC. Neuropharmacology. 2020;162:107836. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    mPFC-to-PVT activity is impaired during social interactions following 2 weeks of adolescent social isolation, and activation of this circuit rescued isolation-induced social deficits.

    “mPFC-to-PVT activity is impaired during social interactions following 2 weeks of adolescent social isolation, and activation of this circuit rescued isolation induced social deficits [166].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [166] Yamamuro K, Bicks LK, Leventhal MB, Kato D, Im S, Flanigan ME, et al. A prefrontal-paraventricular thalamus circuit requires juvenile social experience to regulate adult sociability in mice. Nat Neurosci. 2020;23:1240–52. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intranasal OXT holds some promise for treating social deficits, although it may only be beneficial in subsets of patients with low OXT levels.

    “intranasal OXT holds some promise [172, 173], although it may only be beneficial in subsets of patients with low OXT levels [174].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [172] Ford CL, Young LJ. Refining oxytocin therapy for autism: context is key. Nat Rev Neurol. 2022;18:67–8. source

      Not checked in the free run.

    • cites [173] Aishworiya R, Valica T, Hagerman R, Restrepo B. An update on psychopharmacological treatment of autism spectrum disorder. Neurotherapeutics. 2022;19:248–62. source

      Not checked in the free run.

    • cites [174] Parker KJ, Oztan O, Libove RA, Sumiyoshi RD, Jackson LP, Karhson DS, et al. Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc Natl Acad Sci USA. 2017;114:8119–24. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Standard treatments such as SSRIs or SNRIs, when effective in treating depression, likely ameliorate sociability deficits, but are commonly ineffective in treating large proportions of subjects with mood disorders.

    “It is likely that when effective in treating depression, standard treatments such as selective 5-HT reuptake inhibitors (SSRIs) or 5-HT and norepinephrine reuptake inhibitors (SNRIs) ameliorate sociability deficits but these are all too commonly ineffective in treating large proportions of subjects with mood disorders [3,170,171].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [3] Charney DS, Sklar PB, Buxbaum JD, Nestler EJ. Charney & Nestler’s neurobiology of mental illness. 5th ed. New York: Oxford University Press; 2018. source

      Not checked in the free run.

    • cites [170] King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry. 2009;66:583–90. source

      Not checked in the free run.

    • cites [171] Williams K, Brignell A, Randall M, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2013;8:CD004677.

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Activation of 5-HT1b receptors in the NAc is critical for promoting sociability, while these same receptors in the MS play a critical role in social memory.

    “We have presented evidence that activation of 5-HT1b receptors in the NAc is critical for promoting sociability while these same receptors in the MS play a critical role in social memory.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    Oxytocin stimulates NAc-projecting dopamine neurons in the VTA.

    “Oxytocin also stimulates NAc-projecting dopamine (DA) neurons in the ventral tegmental area (VTA).”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    DA acting on D1 receptors on NAc D1 MSNs is necessary for normal social interactions.

    “Furthermore, DA acting on D1 receptors (D1R) presumably on NAc D1 MSNs is necessary for normal social interactions.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Many neuromodulators and distinct brain regions and circuits have been implicated in the variety of adaptive prosocial behaviors examined in rodents.

    “it is not surprising that many neuromodulators and distinct brain regions and circuits have been implicated in the variety of adaptive prosocial behaviors that have been examined in rodents.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    DA depresses glutamate release only from PVT inputs, potentially via presynaptic D2 receptors.

    “In contrast, DA depresses glutamate release only from PVT inputs, potentially via actions on presynaptic D2 receptors (D2R).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    5-HT filters incoming information to the NAc by depressing glutamate release from excitatory inputs from PVT, vHip, and BLA via 5-HT1b receptors but does not affect mPFC inputs.

    “5-HT also filters incoming information to the NAc by depressing glutamate release from excitatory inputs coming from the paraventricular nucleus of the thalamus (PVT), ventral hippocampus (vHip), and basolateral amygdala (BLA) via 5-HT1b receptors but does not affect medial prefrontal (mPFC) inputs.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    5-HT release in the NAc can regulate oxytocin release via 5-HT4 receptors on PVN inputs.

    “5-HT release in the NAc paradoxically can regulate oxytocin release via 5-HT4 receptors (5-HT4R) on PVN inputs.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Wireless stimulation of PVN OXT neurons in mice enhances both prosocial and agnostic behavior in a context-dependent manner.

    “wireless stimulation of paraventricular hypothalamic nucleus (PVN) OXT neurons in mice was found to enhance both prosocial and agnostic behavior in a contextdependent manner [189].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [189] Anpilov S, Shemesh Y, Eren N, Harony-Nicolas H, Benjamin A, Dine J, et al. Wireless optogenetic stimulation of oxytocin neurons in a semi-natural setup dynamically elevates both pro-social and agonistic behaviors. Neuron. 2020;107:644–55.e7. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Interpretationnone given

    Oxytocin release from PVN inputs to the NAc promotes serotonin release via binding to oxytocin receptors on 5-HT inputs from the DR.

    “Oxytocin release from paraventricular nucleus (PVN) inputs to the NAc promotes serotonin (5-HT) release via binding to oxytocin receptors (OXTR) on 5-HT inputs from the dorsal raphe (DR).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    One case study reported DBS of the BLA in a young self-injurious male with ASD to be effective in blocking self-injury and improving social behavior.

    “we were able to find one case study reporting DBS of the BLA in a young self-injurious male with ASD to be effective in blocking self-injury and improving social behavior [185].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [185] Sturm V, Fricke O, Buhrle CP, Lenartz D, Maarouf M, Treuer H, et al. DBS in the basolateral amygdala improves symptoms of autism and related self-injurious behavior: a case report and hypothesis on the pathogenesis of the disorder. Front Hum Neurosci. 2012;6:341.

      Not checked in the free run.

63 of 63

  • The paper relies on this without support.

    Positive, prosocial interactions are essential for survival, development, and well-being.

    “Positive, prosocial interactions are essential for survival, development, and well-being.”

  • The paper relies on this without support.

    Many neural mechanisms mediating adaptive social behaviors necessary for reproduction and survival have been evolutionarily conserved.

    “It is likely that many of the neural mechanisms mediating adaptive social behaviors that are necessary for reproduction and survival have been evolutionarily conserved.”

  • The paper relies on this without support.

    The ability to recognize and remember individuals is critical to the formation and maintenance of social relationships.

    “The ability to recognize and remember individuals is critical to the formation and maintenance of social relationships.”

  • The paper relies on this without support.

    Mice are social creatures and provide an excellent species in which to investigate the neural circuit mechanisms underlying normal prosocial interactions and disease states.

    “Mice are social creatures and provide an excellent species in which to investigate the neural circuit mechanisms underlying normal prosocial interactions as well as what goes awry in disease states because of their genetic accessibility, which has led to the generation of abundant knockout and transgenic lines.”

  • The paper relies on this without support.

    The use of a juvenile mouse as the object of the adult mouse's attention greatly reduces the likelihood of aggression.

    “The use of a juvenile mouse as the object of the adult mouse's attention greatly reduces the likelihood of aggression.”

  • The paper relies on this without support.

    ASD etiology has a strong genetic component.

    “Because ASD etiology has a strong genetic component”

  • The paper relies on this without support.

    One of the most common etiologies of ASD is a CNV on chromosome 16p11.2.

    “One of the most common etiologies of ASD is a CNV on chromosome 16p11.2.”

  • The paper relies on this without support.

    Stress-related disorders, in particular depression, are frequently accompanied by deficits in adaptive prosocial behaviors.

    “Stress-related disorders, in particular depression, are frequently accompanied by deficits in adaptive prosocial behaviors.”

  • The paper relies on this without support.

    Current pharmacological therapies for neuropsychiatric disorders do not routinely treat discrete behavioral impairments.

    “Current pharmacological therapies for neuropsychiatric disorders do not routinely treat discrete behavioral impairments.”

  • The paper relies on this without support.

    For ASD, there are no approved medications for any of the core symptoms including sociability deficits.

    “For ASD, there are no approved medications for any of the core symptoms including sociability deficits.”

  • The paper relies on this without support.

    Anti-psychotics used to treat SZ have minimal effects on negative symptoms, a prominent one of which is social isolation and withdrawal.

    “Similarly, the anti-psychotics used to treat SZ have minimal effects on negative symptoms, a prominent one of which is social isolation and withdrawal.”

  • The paper relies on this without support.

    Deeper subcortical structures have been implicated in mediating prosocial behaviors and social memory.

    “which have been implicated in mediating prosocial behaviors and social memory.”

  • The paper relies on this without support.

    DBS is used routinely to treat Parkinson's disease and is actively being investigated for its efficacy in depression and obsessive compulsive disorder.

    “Although DBS is used routinely to treat Parkinson's disease and is actively being investigated for its efficacy in depression and obsessive compulsive disorder”

  • The paper relies on this without support.

    To date there are no direct investigations of the circuit mechanism underlying the social transfer of stress phenotype.

    “To date there is no direct investigations of the circuit mechanism underlying this phenotype;”

  • The paper relies on this without support.

    Little research to date has identified the neural mechanisms underlying the reduced social motivation accompanying substance use disorder.

    “However, little research to date has identified the neural mechanisms underlying the reduced social motivation accompanying substance use disorder.”
15 of 15

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 promotes prosocial behavior, bonding, and the saliency of social cues in humans and other mammals.

    “Research in humans and in other mammals demonstrates a role for OT in promoting prosocial behavior, bonding, and the saliency of social cues [9,23,24].”

    From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [24]

    The Introduction describes oxytocin as important for mammalian social and affiliative behavior and reports that blocking its receptors prevents pair bonding in prairie voles. The Neural Mechanisms of Prosocial Behavior and Social Reward section also reports impaired social reward processing when oxytocin receptors are blocked in mice. These passages support the mammalian behavior and bonding claims, but the paper does not establish the claimed effects on the salience of social cues in humans and other mammals, or present human evidence for the full claim. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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.

  • Vasopressin predictor described as peripheral despite CSF citation

    Minor

    The text describes peripheral vasopressin levels as a predictor of ASD, but the cited study identifies the predictor as neonatal cerebrospinal fluid (CSF) vasopressin concentration. CSF is not a peripheral measurement.

1 of 1

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Authors
Walsh, J. J., Christoffel, D. J., & Malenka, R. C.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • Stanford Medicine (US)
Corresponding author
  • Walsh, Jessica J.
  • Malenka, Robert C.
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2022-06-14
Volume
48
Issue
1
Pages
79-89
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/s41386-022-01348-8
PMC
PMC9700801
OpenAlex
W4282828606
Semantic Scholar
596138897f684f4eb545bc0652d9f6252df69e16
Cited by
72
References
191
Citations by year
2026: 12 · 2025: 17 · 2024: 17 · 2023: 17 · 2022: 9
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (MH103949)
  • U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK115985)
  • U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (DA042012)
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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
prosocial behavior, neural circuits, oxytocin, serotonin, dopamine, synaptic transmission, social dysfunction, neuropsychiatric disorders, rodent models, targeted therapeutics
MeSH terms
Altruism, Brain, Dopamine, Synaptic Transmission, Oxytocin, Social Behavior

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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