1. Chen P, Hong W. Neural circuit mechanisms of social behavior. Neuron.
2018;98:16–30.
2. Anderson DJ. Circuit modules linking internal states and social behaviour in flies
and mice. Nat Rev Neurosci. 2016;17:692–704.
3. Wei D, Talwar V, Lin D. Neural circuits of social behaviors: innate yet flexible.
Neuron. 2021;109:1600–20.
4. Wu YE, Hong W. Neural basis of prosocial behavior. Trends Neurosci.
2022;45:749–62.
5. Miura I, Overton ETN, Nakai N, Kawamata T, Sato M, Takumi T. Imaging the
neural circuit basis of social behavior: insights from mouse and human studies.
Neurol Med Chir (Tokyo). 2020;60:429–38.
6. Takumi T, Tamada K, Hatanaka F, Nakai N, Bolton PF. Behavioral neuroscience of
autism. Neurosci Biobehav Rev. 2020;110:60–76.
7. Nakai N, Takumi T, Nakai J, Sato M. Common defects of spine dynamics and
circuit function in neurodevelopmental disorders: a systematic review of findings from in vivo optical imaging of mouse models. Front Neurosci. 2018;12:412.
8. Huguet G, Ey E, Bourgeron T. The genetic landscapes of autism spectrum disorders. Annu Rev Genom Hum Genet. 2013;14:191–213.
9. Takumi T, Tamada K. CNV biology in neurodevelopmental disorders. Curr Opin
Neurobiol. 2018;48:183–92.
M. Sato et al.
10
10. Kim SW, Kim M, Shin HS. Affective empathy and prosocial behavior in rodents.
Curr Opin Neurobiol. 2021;68:181–9.
11. Ko J. Neuroanatomical substrates of rodent social behavior: the medial prefrontal cortex and its projection patterns. Front Neural Circuits. 2017;11:41.
12. Amodio DM, Frith CD. Meeting of minds: the medial frontal cortex and social
cognition. Nat Rev Neurosci. 2006;7:268–77.
13. Klein-Flügge MC, Bongioanni A, Rushworth MFS. Medial and orbital frontal
cortex in decision-making and flexible behavior. Neuron. 2022;110:2743–70.
14. Yizhar O, Levy DR. The social dilemma: prefrontal control of mammalian
sociability. Curr Opin Neurobiol. 2021;68:67–75.
15. Lee E, Rhim I, Lee JW, Ghim JW, Lee S, Kim E, et al. Enhanced neuronal activity in
the medial prefrontal cortex during social approach behavior. J Neurosci.
2016;36:6926–36.
16. Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O’Shea DJ, et al. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature. 2011;477:171–8.
17. Liang B, Zhang L, Barbera G, Fang W, Zhang J, Chen X, et al. Distinct and
dynamic ON and OFF neural ensembles in the prefrontal cortex code social
exploration. Neuron. 2018;100:700–14.
18. Murugan M, Jang HJ, Park M, Miller EM, Cox J, Taliaferro JP, et al. Combined
social and spatial coding in a descending projection from the prefrontal cortex.
Cell. 2017;171:1663–77.
19. Huang WC, Zucca A, Levy J, Page DT. Social behavior is modulated by valenceencoding mPFC-amygdala sub-circuitry. Cell Rep. 2020;32:107899.
20. Felix-Ortiz AC, Burgos-Robles A, Bhagat ND, Leppla CA, Tye KM. Bidirectional
modulation of anxiety-related and social behaviors by amygdala projections to
the medial prefrontal cortex. Neuroscience. 2016;321:197–209.
21. Kuga N, Abe R, Takano K, Ikegaya Y, Sasaki T. Prefrontal-amygdalar oscillations
related to social behavior in mice. eLife. 2022;11:e78428.
22. Liu L, Xu H, Wang J, Li J, Tian Y, Zheng J, et al. Cell type-differential modulation
of prefrontal cortical GABAergic interneurons on low gamma rhythm and social
interaction. Sci Adv. 2020;6:eaay4073.
23. Kim Y, Venkataraju KU, Pradhan K, Mende C, Taranda J, Turaga SC, et al. Mapping social behavior-induced brain activation at cellular resolution in the mouse.
Cell Rep. 2015;10:292–305.
24. Nakajima M, Görlich A, Heintz N. Oxytocin modulates female sociosexual
behavior through a specific class of prefrontal cortical interneurons. Cell.
2014;159:295–305.
25. 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.
26. Park G, Ryu C, Kim S, Jeong SJ, Koo JW, Lee YS, et al. Social isolation impairs the
prefrontal-nucleus accumbens circuit subserving social recognition in mice. Cell
Rep. 2021;35:109104.
27. Benekareddy M, Stachniak TJ, Bruns A, Knoflach F, von Kienlin M, Künnecke B,
et al. Identification of a corticohabenular circuit regulating socially directed
behavior. Biol Psychiatry. 2018;83:607–17.
28. Yang Y, Wang H, Hu J, Hu H. Lateral habenula in the pathophysiology of
depression. Curr Opin Neurobiol. 2018;48:90–6.
29. Kaminska B, Caballero JP, Moorman DE. Integration of value and action in
medial prefrontal neural systems. Int Rev Neurobiol. 2021;158:57–82.
30. Gangopadhyay P, Chawla M, Dal Monte O, Chang SWC. Prefrontal-amygdala
circuits in social decision-making. Nat Neurosci. 2021;24:5–18.
31. Jiang YH, Ehlers MD. Modeling autism by SHANK gene mutations in mice.
Neuron. 2013;78:8–27.
32. Kim S, Kim YE, Song I, Ujihara Y, Kim N, Jiang YH, et al. Neural circuit
pathology driven by Shank3 mutation disrupts social behaviors. Cell Rep.
2022;39:110906.
33. Li Y, Missig G, Finger BC, Landino SM, Alexander AJ, Mokler EL, et al. Maternal
and early postnatal immune activation produce dissociable effects on neurotransmission in mPFC-amygdala circuits. J Neurosci. 2018;38:3358–72.
34. DeSpenza T Jr., Carlson M, Panchagnula S, Robert S, Duy PQ, Mermin-Bunnell N,
et al. PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets. Trends Neurosci.
2021;44:961–76.
35. Huang WC, Chen Y, Page DT. Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome. Nat
Commun. 2016;7:13421.
36. Molosh AI, Johnson PL, Spence JP, Arendt D, Federici LM, Bernabe C, et al. Social
learning and amygdala disruptions in Nf1 mice are rescued by blocking p21activated kinase. Nat Neurosci. 2014;17:1583–90.
37. Nakai N, Otsuka S, Myung J, Takumi T. Autism spectrum disorder model mice:
focus on copy number variation and epigenetics. Sci China Life Sci.
2015;58:976–84.
38. Qin L, Ma K, Wang ZJ, Hu Z, Matas E, Wei J, et al. Social deficits in Shank3deficient mouse models of autism are rescued by histone deacetylase (HDAC)
inhibition. Nat Neurosci. 2018;21:564–75.
39. van Heukelum S, Mars RB, Guthrie M, Buitelaar JK, Beckmann CF, Tiesinga PHE,
et al. Where is cingulate cortex? A cross-species view. Trends Neurosci.
2020;43:285–99.
40. Apps MA, Rushworth MF, Chang SW. The anterior cingulate gyrus and social
cognition: tracking the motivation of others. Neuron. 2016;90:692–707.
41. Chang SW, Gariépy JF, Platt ML. Neuronal reference frames for social decisions
in primate frontal cortex. Nat Neurosci. 2013;16:243–50.
42. Amir N, Klumpp H, Elias J, Bedwell JS, Yanasak N, Miller LS. Increased activation
of the anterior cingulate cortex during processing of disgust faces in individuals
with social phobia. Biol Psychiatry. 2005;57:975–81.
43. Klumpp H, Fitzgerald JM, Kinney KL, Kennedy AE, Shankman SA, Langenecker SA,
et al. Predicting cognitive behavioral therapy response in social anxiety disorder
with anterior cingulate cortex and amygdala during emotion regulation. Neuroimage Clin. 2017;15:25–34.
44. de Waal FBM, Preston SD. Mammalian empathy: behavioural manifestations and
neural basis. Nat Rev Neurosci. 2017;18:498–509.
45. Carcea I, Froemke RC. Biological mechanisms for observational learning. Curr
Opin Neurobiol. 2019;54:178–85.
46. Keum S, Shin HS. Neural basis of observational fear learning: a potential model
of affective empathy. Neuron. 2019;104:78–86.
47. 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.
48. 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.
49. Kim SW, Kim M, Baek J, Latchoumane CF, Gangadharan G, Yoon Y, et al.
Hemispherically lateralized rhythmic oscillations in the cingulate-amygdala circuit drive affective empathy in mice. Neuron. 2023;111:418–29.
50. Smith ML, Asada N, Malenka RC. Anterior cingulate inputs to nucleus accumbens control the social transfer of pain and analgesia. Science. 2021;371:153–9.
51. 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.
52. Gogolla N. The insular cortex. Curr Biol. 2017;27:R580–6.
53. Livneh Y, Andermann ML. Cellular activity in insular cortex across seconds to
hours: sensations and predictions of bodily states. Neuron. 2021;109:3576–93.
54. Allen GV, Saper CB, Hurley KM, Cechetto DF. Organization of visceral and limbic
connections in the insular cortex of the rat. J Comp Neurol. 1991;311:1–16.
55. Shi CJ, Cassell MD. Cortical, thalamic, and amygdaloid connections of the
anterior and posterior insular cortices. J Comp Neurol. 1998;399:440–68.
56. Gogolla N, Takesian AE, Feng G, Fagiolini M, Hensch TK. Sensory integration in
mouse insular cortex reflects GABA circuit maturation. Neuron. 2014;83:894–905.
57. Rodgers KM, Benison AM, Klein A, Barth DS. Auditory, somatosensory, and
multisensory insular cortex in the rat. Cereb Cortex. 2008;18:2941–51.
58. Klein AS, Dolensek N, Weiand C, Gogolla N. Fear balance is maintained by bodily
feedback to the insular cortex in mice. Science. 2021;374:1010–5.
59. Koren T, Yifa R, Amer M, Krot M, Boshnak N, Ben-Shaanan TL, et al. Insular cortex
neurons encode and retrieve specific immune responses. Cell. 2021;184:5902–15.
60. Jasmin L, Rabkin SD, Granato A, Boudah A, Ohara PT. Analgesia and hyperalgesia
from GABA-mediated modulation of the cerebral cortex. Nature. 2003;424:316–20.
61. Tan LL, Pelzer P, Heinl C, Tang W, Gangadharan V, Flor H, et al. A pathway from
midcingulate cortex to posterior insula gates nociceptive hypersensitivity. Nat
Neurosci. 2017;20:1591–601.
62. Chen X, Gabitto M, Peng Y, Ryba NJ, Zuker CS. A gustotopic map of taste
qualities in the mammalian brain. Science. 2011;333:1262–6.
63. Fletcher ML, Ogg MC, Lu L, Ogg RJ, Boughter JD Jr. Overlapping representation
of primary tastes in a defined region of the gustatory cortex. J Neurosci.
2017;37:7595–605.
64. Chen K, Kogan JF, Fontanini A. Spatially distributed representation of taste
quality in the gustatory insular cortex of behaving mice. Curr Biol.
2021;31:247–56.
65. Lavi K, Jacobson GA, Rosenblum K, Lüthi A. Encoding of conditioned taste
aversion in cortico-amygdala circuits. Cell Rep. 2018;24:278–83.
66. Zhu J, Cheng Q, Chen Y, Fan H, Han Z, Hou R, et al. Transient delay-period
activity of agranular insular cortex controls working memory maintenance in
learning novel tasks. Neuron. 2020;105:934–46.
67. Yiannakas A, Kolatt Chandran S, Kayyal H, Gould N, Khamaisy M, Rosenblum K.
Parvalbumin interneuron inhibition onto anterior insula neurons projecting to
the basolateral amygdala drives aversive taste memory retrieval. Curr Biol.
2021;31:2770–84.
Molecular Psychiatry
M. Sato et al.
11
68. Dolensek N, Gehrlach DA, Klein AS, Gogolla N. Facial expressions of emotion
states and their neuronal correlates in mice. Science. 2020;368:89–94.
69. Deng H, Xiao X, Yang T, Ritola K, Hantman A, Li Y, et al. A genetically defined
insula-brainstem circuit selectively controls motivational vigor. Cell.
2021;184:6344–60.
70. Wang L, Gillis-Smith S, Peng Y, Zhang J, Chen X, Salzman CD, et al. The coding of
valence and identity in the mammalian taste system. Nature. 2018;558:127–31.
71. Livneh Y, Ramesh RN, Burgess CR, Levandowski KM, Madara JC, Fenselau H, et al.
Homeostatic circuits selectively gate food cue responses in insular cortex.
Nature. 2017;546:611–6.
72. Livneh Y, Sugden AU, Madara JC, Essner RA, Flores VI, Sugden LA, et al. Estimation of current and future physiological states in insular cortex. Neuron.
2020;105:1094–111.
73. Gehrlach DA, Dolensek N, Klein AS, Roy Chowdhury R, Matthys A, Junghänel M,
et al. Aversive state processing in the posterior insular cortex. Nat Neurosci.
2019;22:1424–37.
74. Wu Y, Chen C, Chen M, Qian K, Lv X, Wang H, et al. The anterior insular cortex
unilaterally controls feeding in response to aversive visceral stimuli in mice. Nat
Commun. 2020;11:640.
75. Miura I, Sato M, Overton ETN, Kunori N, Nakai J, Kawamata T, et al. Encoding of
social exploration by neural ensembles in the insular cortex. PLoS Biol.
2020;18:e3000584.
76. Ramos-Prats A, Paradiso E, Castaldi F, Sadeghi M, Mir MY, Hörtnagl H, et al. VIPexpressing interneurons in the anterior insular cortex contribute to sensory
processing to regulate adaptive behavior. Cell Rep. 2022;39:110893.
77. 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.
78. Rogers-Carter MM, Djerdjaj A, Gribbons KB, Varela JA, Christianson JP. Insular
cortex projections to nucleus accumbens core mediate social approach to
stressed juvenile rats. J Neurosci. 2019;39:8717–29.
79. Zhang MM, Geng AQ, Chen K, Wang J, Wang P, Qiu XT, et al. Glutamatergic
synapses from the insular cortex to the basolateral amygdala encode observational pain. Neuron. 2022;110:1993–2008.
80. Craig AD. How do you feel-now? The anterior insula and human awareness. Nat
Rev Neurosci. 2009;10:59–70.
81. Uddin LQ. Salience processing and insular cortical function and dysfunction. Nat
Rev Neurosci. 2015;16:55–61.
82. Nomi JS, Molnar-Szakacs I, Uddin LQ. Insular function in autism: update and
future directions in neuroimaging and interventions. Prog Neuropsychopharmacol Biol Psychiatry. 2019;89:412–26.
83. Mow JL, Gandhi A, Fulford D. Imaging the “social brain” in schizophrenia: a
systematic review of neuroimaging studies of social reward and punishment.
Neurosci Biobehav Rev. 2020;118:704–22.
84. Gehrlach DA, Weiand C, Gaitanos TN, Cho E, Klein AS, Hennrich AA, et al. A
whole-brain connectivity map of mouse insular cortex. eLife. 2020;9:e55585.
85. O’Connell LA, Hofmann HA. The vertebrate mesolimbic reward system and
social behavior network: a comparative synthesis. J Comp Neurol.
2011;519:3599–639.
86. O’Connell LA, Hofmann HA. Evolution of a vertebrate social decision-making
network. Science. 2012;336:1154–7.
87. Newman SW. The medial extended amygdala in male reproductive behavior. A
node in the mammalian social behavior network. Ann N. Y Acad Sci.
1999;877:242–57.
88. Rogers-Carter MM, Christianson JP. An insular view of the social decision-making
network. Neurosci Biobehav Rev. 2019;103:119–32.
89. Bird CW, Barto D, Magcalas CM, Rodriguez CI, Donaldson T, Davies S, et al.
Ifenprodil infusion in agranular insular cortex alters social behavior and vocalizations in rats exposed to moderate levels of ethanol during prenatal development. Behav Brain Res. 2017;320:1–11.
90. Lockwood PL. The anatomy of empathy: vicarious experience and disorders of
social cognition. Behav Brain Res. 2016;311:255–66.
91. Langford DJ, Crager SE, Shehzad Z, Smith SB, Sotocinal SG, Levenstadt JS, et al.
Social modulation of pain as evidence for empathy in mice. Science.
2006;312:1967–70.
92. Zaniboni CR, Pelarin V, Baptista-de-Souza D, Canto-de-Souza A. Empathy for
pain: insula inactivation and systemic treatment with midazolam reverses the
hyperalgesia induced by cohabitation with a pair in chronic pain condition.
Front Behav Neurosci. 2018;12:278.
93. Burkett JP, Andari E, Johnson ZV, Curry DC, de Waal FB, Young LJ. Oxytocindependent consolation behavior in rodents. Science. 2016;351:375–8.
94. Matsumoto M, Yoshida M, Jayathilake BW, Inutsuka A, Nishimori K, Takayanagi Y,
et al. Indispensable role of the oxytocin receptor for allogrooming toward socially
distressed cage mates in female mice. J Neuroendocrinol. 2021;33:e12980.
Molecular Psychiatry
95. Wu YE, Dang J, Kingsbury L, Zhang M, Sun F, Hu RK, et al. Neural control of
affiliative touch in prosocial interaction. Nature. 2021;599:262–7.
96. Ben-Ami Bartal I, Decety J, Mason P. Empathy and pro-social behavior in rats.
Science. 2011;334:1427–30.
97. Cox SS, Kearns AM, Woods SK, Brown BJ, Brown SJ, Reichel CM. The role of the
anterior insular during targeted helping behavior in male rats. Sci Rep.
2022;12:3315.
98. Singer T, Seymour B, O’Doherty J, Kaube H, Dolan RJ, Frith CD. Empathy for pain
involves the affective but not sensory components of pain. Science.
2004;303:1157–62.
99. Lamm C, Decety J, Singer T. Meta-analytic evidence for common and distinct
neural networks associated with directly experienced pain and empathy for
pain. Neuroimage. 2011;54:2492–502.
100. Wicker B, Keysers C, Plailly J, Royet JP, Gallese V, Rizzolatti G. Both of us disgusted in my insula: the common neural basis of seeing and feeling disgust.
Neuron. 2003;40:655–64.
101. Gu X, Gao Z, Wang X, Liu X, Knight RT, Hof PR, et al. Anterior insular cortex is
necessary for empathetic pain perception. Brain. 2012;135:2726–35.
102. Aoki Y, Yahata N, Watanabe T, Takano Y, Kawakubo Y, Kuwabara H, et al. Oxytocin improves behavioural and neural deficits in inferring others’ social emotions in autism. Brain. 2014;137:3073–86.
103. Djerdjaj A, Ng AJ, Rieger NS, Christianson JP. The basolateral amygdala to
posterior insular cortex tract is necessary for social interaction with stressed
juvenile rats. Behav Brain Res. 2022;435:114050.
104. McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, Crawley JN. Autism-like
behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav. 2008;7:152–63.
105. Froemke RC, Young LJ. Oxytocin, neural plasticity, and social behavior. Annu Rev
Neurosci. 2021;44:359–81.
106. Knobloch HS, Charlet A, Hoffmann LC, Eliava M, Khrulev S, Cetin AH, et al.
Evoked axonal oxytocin release in the central amygdala attenuates fear
response. Neuron. 2012;73:553–66.
107. Son S, Manjila SB, Newmaster KT, Wu YT, Vanselow DJ, Ciarletta M, et al. Wholebrain wiring diagram of oxytocin system in adult mice. J Neurosci.
2022;42:5021–33.
108. Ferguson JN, Young LJ, Hearn EF, Matzuk MM, Insel TR, Winslow JT. Social
amnesia in mice lacking the oxytocin gene. Nat Genet. 2000;25:284–8.
109. Takayanagi Y, Yoshida M, Bielsky IF, Ross HE, Kawamata M, Onaka T, et al.
Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient
mice. Proc Natl Acad Sci USA. 2005;102:16096–101.
110. Ferguson JN, Aldag JM, Insel TR, Young LJ. Oxytocin in the medial amygdala is
essential for social recognition in the mouse. J Neurosci. 2001;21:8278–85.
111. Raam T, McAvoy KM, Besnard A, Veenema AH, Sahay A. Hippocampal oxytocin
receptors are necessary for discrimination of social stimuli. Nat Commun.
2017;8:2001.
112. Marlin BJ, Mitre M, D’Amour JA, Chao MV, Froemke RC. Oxytocin enables
maternal behaviour by balancing cortical inhibition. Nature. 2015;520:
499–504.
113. Young LJ, Lim MM, Gingrich B, Insel TR. Cellular mechanisms of social attachment. Horm Behav. 2001;40:133–8.
114. Hung LW, Neuner S, Polepalli JS, Beier KT, Wright M, Walsh JJ, et al. Gating of social
reward by oxytocin in the ventral tegmental area. Science. 2017;357:1406–11.
115. Dölen G, Darvishzadeh A, Huang KW, Malenka RC. Social reward requires
coordinated activity of nucleus accumbens oxytocin and serotonin. Nature.
2013;501:179–84.
116. Salgado S, Kaplitt MG. The nucleus accumbens: a comprehensive review. Stereotact Funct Neurosurg. 2015;93:75–93.
117. 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.
118. Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, et al. Molecular
adaptations underlying susceptibility and resistance to social defeat in brain
reward regions. Cell. 2007;131:391–404.
119. 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.
120. Muir J, Lorsch ZS, Ramakrishnan C, Deisseroth K, Nestler EJ, Calipari ES, et al. In
vivo fiber photometry reveals signature of future stress susceptibility in nucleus
accumbens. Neuropsychopharmacology. 2018;43:255–63.
121. Brumback AC, Ellwood IT, Kjaerby C, Iafrati J, Robinson S, Lee AT, et al. Identifying
specific prefrontal neurons that contribute to autism-associated abnormalities in
physiology and social behavior. Mol Psychiatry. 2018;23:2078–89.
122. Challis C, Beck SG, Berton O. Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective
choices after social defeat. Front Behav Neurosci. 2014;8:43.
M. Sato et al.
12
123. Cavalcante LES, Zinn CG, Schmidt SD, Saenger BF, Ferreira FF, Furini CRG, et al.
Modulation of the storage of social recognition memory by neurotransmitter
systems in the insular cortex. Behav Brain Res. 2017;334:129–34.
124. 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.
125. 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.
126. Isles AR, Ingason A, Lowther C, Walters J, Gawlick M, Stöber G, et al. Parental
origin of interstitial duplications at 15q11.2-q13.3 in Schizophrenia and neurodevelopmental disorders. PLoS Genet. 2016;12:e1005993.
127. Nakatani J, Tamada K, Hatanaka F, Ise S, Ohta H, Inoue K, et al. Abnormal
behavior in a chromosome-engineered mouse model for human 15q11-13
duplication seen in autism. Cell. 2009;137:1235–46.
128. Tamada K, Tomonaga S, Hatanaka F, Nakai N, Takao K, Miyakawa T, et al.
Decreased exploratory activity in a mouse model of 15q duplication syndrome;
implications for disturbance of serotonin signaling. PLoS One. 2010;5:e15126.
129. Chung C, Shin W, Kim E. Early and late corrections in mouse models of autism
spectrum disorder. Biol Psychiatry. 2022;91:934–44.
130. Yin X, Jones N, Yang J, Asraoui N, Mathieu ME, Cai L, et al. Delayed motor
learning in a 16p11.2 deletion mouse model of autism is rescued by locus
coeruleus activation. Nat Neurosci. 2021;24:646–57.
131. Zhang HF, Dai YC, Wu J, Jia MX, Zhang JS, Shou XJ, et al. Plasma oxytocin and
Arginine-Vasopressin levels in children with autism spectrum disorder in China:
associations with symptoms. Neurosci Bull. 2016;32:423–32.
132. Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D. Oxytocin receptor
genetic variation relates to empathy and stress reactivity in humans. Proc Natl
Acad Sci USA. 2009;106:21437–41.
133. LoParo D, Waldman ID. The oxytocin receptor gene (OXTR) is associated with
autism spectrum disorder: a meta-analysis. Mol Psychiatry. 2015;20:640–6.
134. Jin D, Liu HX, Hirai H, Torashima T, Nagai T, Lopatina O, et al. CD38 is critical for
social behaviour by regulating oxytocin secretion. Nature. 2007;446:41–45.
135. Fujima S, Yamaga R, Minami H, Mizuno S, Shinoda Y, Sadakata T, et al. CAPS2
deficiency impairs the release of the social peptide oxytocin, as well as oxytocinassociated social behavior. J Neurosci. 2021;41:4524–35.
136. Peñagarikano O, Lázaro MT, Lu XH, Gordon A, Dong H, Lam HA, et al. Exogenous
and evoked oxytocin restores social behavior in the Cntnap2 mouse model of
autism. Sci Transl Med. 2015;7:271ra278.
137. Sgritta M, Dooling SW, Buffington SA, Momin EN, Francis MB, Britton RA, et al.
Mechanisms underlying microbial-mediated changes in social behavior in
mouse models of autism spectrum disorder. Neuron. 2019;101:246–59.
138. Harony-Nicolas H, Kay M, du Hoffmann J, Klein ME, Bozdagi-Gunal O, Riad M,
et al. Oxytocin improves behavioral and electrophysiological deficits in a novel
Shank3-deficient rat. eLife. 2017;6:e18904.
139. Lewis EM, Stein-O’Brien GL, Patino AV, Nardou R, Grossman CD, Brown M, et al.
Parallel social information processing circuits are differentially impacted in
autism. Neuron. 2020;108:659–75.
140. Hörnberg H, Pérez-Garci E, Schreiner D, Hatstatt-Burklé L, Magara F, Baudouin S,
et al. Rescue of oxytocin response and social behaviour in a mouse model of
autism. Nature. 2020;584:252–6.
141. Bariselli S, Tzanoulinou S, Glangetas C, Prévost-Solié C, Pucci L, Viguié J, et al.
SHANK3 controls maturation of social reward circuits in the VTA. Nat Neurosci.
2016;19:926–34.
142. Choe KY, Bethlehem RAI, Safrin M, Dong H, Salman E, Li Y, et al. Oxytocin
normalizes altered circuit connectivity for social rescue of the Cntnap2 knockout
mouse. Neuron. 2022;110:795–808.
143. Renier N, Adams EL, Kirst C, Wu Z, Azevedo R, Kohl J, et al. Mapping of brain
activity by automated volume analysis of immediate early genes. Cell.
2016;165:1789–802.
144. Johnson ZV, Walum H, Xiao Y, Riefkohl PC, Young LJ. Oxytocin receptors
modulate a social salience neural network in male prairie voles. Horm Behav.
2017;87:16–24.
145. Bosch OJ, Dabrowska J, Modi ME, Johnson ZV, Keebaugh AC, Barrett CE, et al.
Oxytocin in the nucleus accumbens shell reverses CRFR2-evoked passive stresscoping after partner loss in monogamous male prairie voles. Psychoneuroendocrinology. 2016;64:66–78.
146. Mague SD, Talbot A, Blount C, Walder-Christensen KK, Duffney LJ, Adamson E,
et al. Brain-wide electrical dynamics encode individual appetitive social behavior. Neuron. 2022;110:1728–41.
147. Nakai N, Sato M, Yamashita O, Sekine Y, Fu X, Nakai J, et al. Virtual reality-based
real-time imaging reveals abnormal cortical dynamics during behavioral transitions in a mouse model of autism. Cell Rep. 2023;42:112258.
148. Ota K, Oisi Y, Suzuki T, Ikeda M, Ito Y, Ito T, et al. Fast, cell-resolution, contiguouswide two-photon imaging to reveal functional network architectures across
multi-modal cortical areas. Neuron. 2021;109:1810–24.
149. Lecoq J, Savall J, Vučinić D, Grewe BF, Kim H, Li JZ, et al. Visualizing mammalian
brain area interactions by dual-axis two-photon calcium imaging. Nat Neurosci.
2014;17:1825–9.
150. Kingsbury L, Hong W. A multi-brain framework for social interaction. Trends
Neurosci. 2020;43:651–66.
151. Kingsbury L, Huang S, Wang J, Gu K, Golshani P, Wu YE, et al. Correlated neural
activity and encoding of behavior across brains of socially interacting animals.
Cell. 2019;178:429–46.
152. Zhang W, Yartsev MM. Correlated neural activity across the brains of socially
interacting bats. Cell. 2019;178:413–28.
153. Usmani SS, Sharath M, Mehendale M. Future of mental health in the metaverse.
Gen Psychiatr. 2022;35:e100825.
154. Calabrò RS, Cerasa A, Ciancarelli I, Pignolo L, Tonin P, Iosa M, et al. The arrival of
the metaverse in neurorehabilitation: fact, fake or vision? Biomedicines.
2022;10:2602.
155. Lozano AM, Lipsman N, Bergman H, Brown P, Chabardes S, Chang JW, et al.
Deep brain stimulation: current challenges and future directions. Nat Rev
Neurol. 2019;15:148–60.
156. Finisguerra A, Borgatti R, Urgesi C. Non-invasive brain stimulation for the
rehabilitation of children and adolescents with neurodevelopmental disorders: a
systematic review. Front Psychol. 2019;10:135.
157. García-González S, Lugo-Marín J, Setien-Ramos I, Gisbert-Gustemps L, ArteagaHenríquez G, Díez-Villoria E, et al. Transcranial direct current stimulation in
Autism Spectrum Disorder: a systematic review and meta-analysis. Eur Neuropsychopharmacol. 2021;48:89–109.
158. Rosson S, de Filippis R, Croatto G, Collantoni E, Pallottino S, Guinart D, et al. Brain
stimulation and other biological non-pharmacological interventions in mental
disorders: an umbrella review. Neurosci Biobehav Rev. 2022;139:104743.
159. Liu X, Qiu F, Hou L, Wang X. Review of noninvasive or minimally invasive deep
brain stimulation. Front Behav Neurosci. 2021;15:820017.
ACKNOWLEDGEMENTS
We thank Yu Ohmura for his valuable comments on this manuscript.
AUTHOR CONTRIBUTIONS
MS, NN, SF, KYC, and TT wrote and edited the manuscript.
FUNDING
The authors receive financial support from: The KAKENHI from JSPS (20H03550 and
23H02668) and Taiju Life Social Welfare Foundation to MS; The KAKENHI from JSPS
(23K14673 and 23H04138) to NN; The KAKENHI from JSPS (16H06316, 16H06463,
21H00202, 21H04813, and 23H04233), Japan Agency for Medical Research and
Development (JP21wm0425011), Japan Science and Technology Agency (JPMJMS2299
and JPMJMS229B), Intramural Research Grant (30-9) for Neurological and Psychiatric
Disorders of NCNP, The Takeda Science Foundation, Research Foundation for OptoScience and Technology, Taiju Life Social Welfare Foundation, The Naito Foundation,
The Tokumori Yasumoto Memorial Trust for Researches on Tuberous Sclerosis Complex
and Related Rare Neurological Diseases to TT, and the Canada Research Chairs Program
to KYC. Open access funding provided by Kobe University.
COMPETING INTERESTS
The authors declare no competing interests.
ADDITIONAL INFORMATION
Correspondence and requests for materials should be addressed to Toru Takumi.
Reprints and permission information is available at http://www.nature.com/
reprints
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims
in published maps and institutional affiliations.
Molecular Psychiatry
M. Sato et al.
13
Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons licence, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons licence, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directl ...