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The prelimbic prefrontal cortex mediates the development of lasting social avoidance as a consequence of social threat conditioning

Neuropsychopharmacology volume 50, pages 1875–1884 (2025)Cite this article

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Abstract

Social avoidance is highly detrimental for natural behavior. Despite much research on this topic, the mechanisms underlying the development of social avoidance as a consequence of social-related traumatic experiences remain highly elusive. To investigate this issue, we adapted a mouse model of social threat conditioning in which mice received shock punishment during exploration of an unfamiliar conspecific. This resulted in prominent and lasting reductions in social behavior, effects that were not observed in mice that received shock punishment in the absence of a social stimulus. Furthermore, the effects of social threat conditioning were independent of contextual settings, sex variables, and particular identity of the unfamiliar conspecifics that predicted shock punishment. Shedding new light into the neurobiological bases for this phenomenon, we found that optogenetic silencing of the prelimbic (PL), but not infralimbic (IL), prefrontal cortex during social threat conditioning produced profound forgetting and restoration of social behavior during subsequent sociability tests. Significant forgetting and recovery of social behavior was also observed with prelimbic inhibition of NMDARs. Collectively, these findings are consistent with the notion that social-related trauma is a prominent risk factor for social avoidance, and that traumatic experiences that involve social elements engage learning-related mechanisms in corticolimbic networks to promote long-term representations of social threat.

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Fig. 1: Social threat conditioning resulted in robust social avoidance.
Fig. 2: Differential social threat conditioning also resulted in generalized social avoidance.
Fig. 3: Alterations in social behavior after social threat conditioning were enduring, sex-independent, and predominantly exhibited towards unfamiliar conspecifics but not cagemates.
Fig. 4: Photoinhibition of the prelimbic prefrontal cortex prevented the long-term consequences of social threat conditioning.
Fig. 5: Photoinhibition of the adjacent infralimbic prefrontal cortex did not prevent the long-term consequences of social threat conditioning.

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References

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5TM, 5th ed. Arlington, VA, USA: American Psychiatric Publishing, Inc.; 2013.

  2. Rose GM, Tadi P. Social anxiety disorder. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.

  3. Den Boer JA. Social anxiety disorder/social phobia: epidemiology, diagnosis, neurobiology, and treatment. Compr Psychiatry. 2000;41:405–15.

    Article  Google Scholar 

  4. Spence SH, Rapee RM. The etiology of social anxiety disorder: an evidence-based model. Behav Res Ther. 2016;86:50–67.

    Article  PubMed  Google Scholar 

  5. Mizzi S, Pedersen M, Lorenzetti V, Heinrichs M, Labuschagne I. Resting-state neuroimaging in social anxiety disorder: a systematic review. Mol Psychiatry. 2022;27:164–79.

    Article  PubMed  Google Scholar 

  6. Bas-Hoogendam JM, Blackford JU, Brühl AB, Blair KS, van der Wee NJA, Westenberg PM. Neurobiological candidate endophenotypes of social anxiety disorder. Neurosci Biobehav Rev. 2016;71:362–78.

    Article  PubMed  Google Scholar 

  7. Toth I, Neumann ID. Animal models of social avoidance and social fear. Cell Tissue Res. 2013;354:107–18.

    Article  PubMed  Google Scholar 

  8. Haller J, Bakos N. Stress-induced social avoidance: a new model of stress-induced anxiety? Physiol Behav. 2002;77:327–32.

    Article  CAS  PubMed  Google Scholar 

  9. Toth I, Neumann ID, Slattery DA. Social fear conditioning: a novel and specific animal model to study social anxiety disorder. Neuropsychopharmacology. 2012;37:1433–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. McTaggart EM, Miller NW, Ortiz-Juza MM, Pégard NC, Rodriguez-Romaguera J. A fully automated social interaction chamber for studying social threat learning in mice. Front Behav Neurosci. 2024;18:1481935.

  11. Toth I, Neumann ID, Slattery DA. Social fear conditioning as an animal model of social anxiety disorder. Curr Protoc Neurosci. 2013;63:9.42.1-9.42.13.

  12. Brühl AB, Delsignore A, Komossa K, Weidt S. Neuroimaging in social anxiety disorder—a meta-analytic review resulting in a new neurofunctional model. Neurosci Biobehav Rev. 2014;47:260–80.

    Article  PubMed  Google Scholar 

  13. Brühl AB, Hänggi J, Baur V, Rufer M, Delsignore A, Weidt S, et al. Increased cortical thickness in a frontoparietal network in social anxiety disorder. Hum Brain Mapp. 2014;35:2966–77.

    Article  PubMed  Google Scholar 

  14. Buff C, Brinkmann L, Neumeister P, Feldker K, Heitmann C, Gathmann B, et al. Specifically altered brain responses to threat in generalized anxiety disorder relative to social anxiety disorder and panic disorder. NeuroImage Clin. 2016;12:698–706.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Qi C-C, Wang Q-J, Ma X-Z, Chen H-C, Gao L-P, Yin J, et al. Interaction of basolateral amygdala, ventral hippocampus and medial prefrontal cortex regulates the consolidation and extinction of social fear. Behav Brain Funct. 2018;14:7.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Xu H, Liu L, Tian Y, Wang J, Li J, Zheng J, et al. A disinhibitory microcircuit mediates conditioned social fear in the prefrontal cortex. Neuron. 2019;102:668–.e5.

    Article  CAS  PubMed  Google Scholar 

  17. Calhoon GG, Tye KM. Resolving the neural circuits of anxiety. Nat Neurosci. 2015;18:1394–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Campos AC, Fogaça MV, Aguiar DC, Guimarães FS. Animal models of anxiety disorders and stress. Braz J Psychiatry. 2013;35:S101–111.

    Article  PubMed  Google Scholar 

  19. Kraeuter A-K, Guest PC, Sarnyai Z. The open field test for measuring locomotor activity and anxiety-like behavior. Methods Mol Biol. 2019;1916:99–103.

    Article  CAS  PubMed  Google Scholar 

  20. Seibenhener ML, Wooten MC. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp. 2015;6:e52434.

    Google Scholar 

  21. Felix-Ortiz AC, Terrell JM, Gonzalez C, Msengi HD, Boggan MB, Ramos AR, et al. Prefrontal regulation of safety learning during ethologically relevant thermal threat. eNeuro. 2024. https://doi.org/10.1523/ENEURO.0140-23.2024.

  22. Villalon SA, Felix-Ortiz AC, Lozano-Ortiz K, McCarrey JR, Burgos-Robles A. Impacts of social isolation stress in safety learning and the structure of defensive behavior during a spatial-based learning task involving thermal threat. Front Behav Neurosci. 2024;18:1503097.

  23. Xu C, Peng B, Liu S. Using intra-brain drug infusion to investigate neural mechanisms underlying reward-seeking behavior in mice. STAR Protoc. 2022;3:101221.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gruene TM, Flick K, Stefano A, Shea SD, Shansky RM. Sexually divergent expression of active and passive conditioned fear responses in rats. Elife. 2015;4:e11352.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mitchell JR, Trettel SG, Li AJ, Wasielewski S, Huckleberry KA, Fanikos M, et al. Darting across space and time: parametric modulators of sex-biased conditioned fear responses. Learn Mem. 2022;29:171–80.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bolles RC. Avoidance and escape learning: simultaneous acquisition of different responses. J Comp Physiol Psychol. 1969;68:355–8.

    Article  CAS  PubMed  Google Scholar 

  27. Furuyama T, Yamamoto R, Kato N, Ono M. Modified fear conditioning for inducing flight behaviors in mice. J Vis Exp. 2023. https://doi.org/10.3791/66266.

  28. Molewijk HE, van der Poel AM, Olivier B. The ambivalent behaviour ‘stretched approach posture’ in the rat as a paradigm to characterize anxiolytic drugs. Psychopharmacology. 1995;121:81–90.

    Article  CAS  PubMed  Google Scholar 

  29. Yang M, Augustsson H, Markham CM, Hubbard DT, Webster D, Wall PM, et al. The rat exposure test: a model of mouse defensive behaviors. Physiol Behav. 2004;81:465–73.

    Article  CAS  PubMed  Google Scholar 

  30. Holly KS, Orndorff CO, Murray TA. MATSAP: an automated analysis of stretch-attend posture in rodent behavioral experiments. Sci Rep. 2016;6:31286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Burgos-Robles A, Vidal-Gonzalez I, Santini E, Quirk GJ. Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex. Neuron. 2007;53:871–80.

    Article  CAS  PubMed  Google Scholar 

  32. Hansen KB, Yi F, Perszyk RE, Furukawa H, Wollmuth LP, Gibb AJ, et al. Structure, function, and allosteric modulation of NMDA receptors. J General Physiol. 2018;150:1081–105.

    Article  CAS  Google Scholar 

  33. Sotres-Bayon F, Quirk GJ. Prefrontal control of fear: more than just extinction. Curr Opin Neurobiol. 2010;20:231–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bayer H, Bertoglio LJ. Infralimbic cortex controls fear memory generalization and susceptibility to extinction during consolidation. Sci Rep. 2020;10:15827.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Santini E, Quirk GJ, Porter JT. Fear conditioning and extinction differentially modify the intrinsic excitability of infralimbic neurons. J Neurosci. 2008;28:4028–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Vidal-Gonzalez I, Vidal-Gonzalez B, Rauch SL, Quirk GJ. Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learn Mem. 2006;13:728–33.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Boudjafad Z, Lguensat A, Elmardadi K, Dahi A, Bennis M, Ba-M’hamed S, et al. The socially enriched environment test: a new approach to evaluate social behavior in a mouse model of social anxiety disorder. Learn Mem. 2022;29:390–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liebowitz MR, Gorman JM, Fyer AJ, Klein DF. Social phobia. Review of a neglected anxiety disorder. Arch Gen Psychiatry. 1985;42:729–36.

    Article  CAS  PubMed  Google Scholar 

  39. Tei S, Kauppi J-P, Jankowski KF, Fujino J, Monti RP, Tohka J, et al. Brain and behavioral alterations in subjects with social anxiety dominated by empathic embarrassment. Proc Natl Acad Sci USA. 2020;117:4385–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Li D, Chokka P, Tibbo P. Toward an integrative understanding of social phobia. J Psychiatry Neurosci. 2001;26:190–202.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Van Ameringen M, Mancini C, Farvolden P, Oakman J. The neurobiology of social phobia: from pharmacotherapy to brain imaging. Curr Psychiatry Rep. 2000;2:358–66.

    Article  PubMed  Google Scholar 

  42. Bartlett AA, Singh R, Hunter RG. Anxiety and epigenetics. Adv Exp Med Biol. 2017;978:145–66.

    Article  CAS  PubMed  Google Scholar 

  43. Lin E, Tsai S-J. Gene-environment interactions and role of epigenetics in anxiety disorders. Adv Exp Med Biol. 2020;1191:93–102.

    Article  CAS  PubMed  Google Scholar 

  44. Bebchuk JM, Tancer ME. Neurobiology of social phobia. CNS Spectr. 1999;4:42–48.

    Article  CAS  PubMed  Google Scholar 

  45. Wang J, Tian Y, Zeng L-H, Xu H. Prefrontal disinhibition in social fear: a vital action of somatostatin interneurons. Front Cell Neurosci. 2020;14:611732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lucas EK, Clem RL. GABAergic interneurons: The orchestra or the conductor in fear learning and memory? Brain Res Bull. 2018;141:13–19.

    Article  CAS  PubMed  Google Scholar 

  47. Courtin J, Chaudun F, Rozeske RR, Karalis N, Gonzalez-Campo C, Wurtz H, et al. Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression. Nature. 2014;505:92–96.

    Article  PubMed  Google Scholar 

  48. Etkin A, Egner T, Kalisch R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn Sci. 2011;15:85–93.

    Article  PubMed  Google Scholar 

  49. Burgos-Robles A, Vidal-Gonzalez I, Quirk GJ. Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure. J Neurosci. 2009;29:8474–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Allsop SA, Wichmann R, Mills F, Burgos-Robles A, Chang C-J, Felix-Ortiz AC, et al. Corticoamygdala transfer of socially derived information gates observational learning. Cell. 2018;173:1329–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fernandez-Leon JA, Engelke DS, Aquino-Miranda G, Goodson A, Rasheed MN, Do-Monte FH. Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex. eLife. 2021;10:e74950.

  52. Bravo-Rivera C, Sotres-Bayon F. From isolated emotional memories to their competition during conflict. Front Behav Neurosci. 2020;14:36.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Burgos-Robles A, Kimchi EY, Izadmehr EM, Porzenheim MJ, Ramos-Guasp WA, Nieh EH, et al. Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment. Nat Neurosci. 2017;20:824–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Anastasiades PG, Carter AG. Circuit organization of the rodent medial prefrontal cortex. Trends Neurosci. 2021;44:550–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Yang S-S, Mack NR, Shu Y, Gao W-J. Prefrontal GABAergic interneurons gate long-range afferents to regulate prefrontal cortex-associated complex behaviors. Front Neural Circuits. 2021;15:716408.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Jodo E, Katayama T, Okamoto M, Suzuki Y, Hoshino K, Kayama Y. Differences in responsiveness of mediodorsal thalamic and medial prefrontal cortical neurons to social interaction and systemically administered phencyclidine in rats. Neuroscience. 2010;170:1153–64.

    Article  CAS  PubMed  Google Scholar 

  57. Hoover WB, Vertes RP. Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat. Brain Struct Funct. 2007;212:149–79.

    Article  PubMed  Google Scholar 

  58. Zhou T, Zhu H, Fan Z, Wang F, Chen Y, Liang H, et al. History of winning remodels thalamo-PFC circuit to reinforce social dominance. Science. 2017;357:162–8.

    Article  CAS  PubMed  Google Scholar 

  59. Zhou T, Sandi C, Hu H. Advances in understanding neural mechanisms of social dominance. Curr Opin Neurobiol. 2018;49:99–107.

    Article  CAS  PubMed  Google Scholar 

  60. Vander Weele CM, Siciliano CA, Matthews GA, Namburi P, Izadmehr EM, Espinel IC, et al. Dopamine enhances signal-to-noise ratio in cortical-brainstem encoding of aversive stimuli. Nature. 2018;563:397–401.

    Article  Google Scholar 

  61. Jercog D, Winke N, Sung K, Fernandez MM, Francioni C, Rajot D, et al. Dynamical prefrontal population coding during defensive behaviours. Nature. 2021;595:690–4.

    Article  CAS  PubMed  Google Scholar 

  62. Janak PH, Tye KM. From circuits to behaviour in the amygdala. Nature. 2015;517:284–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Johansen JP, Tarpley JW, LeDoux JE, Blair HT. Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray. Nat Neurosci. 2010;13:979–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gore F, Schwartz EC, Brangers BC, Aladi S, Stujenske JM, Likhtik E, et al. Neural representations of unconditioned stimuli in basolateral amygdala mediate innate and learned responses. Cell. 2015;162:134–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wei J-A, Han Q, Luo Z, Liu L, Cui J, Tan J, et al. Amygdala neural ensemble mediates mouse social investigation behaviors. Natl Sci Rev. 2023;10:nwac179.

    Article  CAS  PubMed  Google Scholar 

  66. Gabriel M, Sparenborg S, Kubota Y. Anterior and medial thalamic lesions, discriminative avoidance learning, and cingulate cortical neuronal activity in rabbits. Exp Brain Res. 1989;76:441–57.

    Article  CAS  PubMed  Google Scholar 

  67. Glover EJ, Margaret Starr E, Gascon A, Clayton-Stiglbauer K, Amegashie CL, Selchick AH, et al. Involvement of cortical input to the rostromedial tegmental nucleus in aversion to foot shock. Neuropsychopharmacology. 2023;48:1455–64.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Powell DA, Maxwell B, Penney J. Neuronal activity in the medial prefrontal cortex during Pavlovian eyeblink and nictitating membrane conditioning. J Neurosci. 1996;16:6296–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gilmartin MR, McEchron MD. Single neurons in the medial prefrontal cortex of the rat exhibit tonic and phasic coding during trace fear conditioning. Behav Neurosci. 2005;119:1496–510.

    Article  PubMed  Google Scholar 

  70. Gilmartin MR, Balderston NL, Helmstetter FJ. Prefrontal cortical regulation of fear learning. Trends Neurosciences. 2014;37:455–64.

    Article  CAS  Google Scholar 

  71. Gilmartin MR, Helmstetter FJ. Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex. Learn Mem. 2010;17:289–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Arruda-Carvalho M, Clem RL. Pathway-selective adjustment of prefrontal-amygdala transmission during fear encoding. J Neurosci. 2014;34:15601–9.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Scharnowski F, Nicholson AA, Pichon S, Rosa MJ, Rey G, Eickhoff SB, et al. The role of the subgenual anterior cingulate cortex in dorsomedial prefrontal-amygdala neural circuitry during positive-social emotion regulation. Hum Brain Mapp. 2020;41:3100–18.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Huang W-C, Zucca A, Levy J, Page DT. Social behavior is modulated by valence-encoding mPFC-amygdala sub-circuitry. Cell Rep. 2020;32:107899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Diehl MM, Iravedra-Garcia JM, Morán-Sierra J, Rojas-Bowe G, Gonzalez-Diaz FN, Valentín-Valentín VP, et al. Divergent projections of the prelimbic cortex bidirectionally regulate active avoidance. Elife. 2020;9:e59281.

  76. 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–.e16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank Shatavia McBride and Hope Msengi for technical assistance. The authors would also like to thank Dr. Isabel Muzzio, Dr. Todd Troyer, and Dr. Edwin Barea-Rodriguez for sharing equipment, Dr. Alfonso Apicella for sharing supplies and for general feedback on the project, and Dr. Maria Diehl for comments on an earlier version of the manuscript.

Funding

KLO, ACFO, JMT, CG, KRW, AEK, ARR, SAV, ANM, and ABR were supported by the Baptist Health Foundation, UTSA NDRB Seed Grant Program, UTSA College of Sciences, UT-STAR Program, and NIH grants R25EB027605 and T34GM145507. JRR was supported by the North Carolina TraCS Institute, Foundation of Hope, Brain and Behavior Research Foundation, Kavli Foundation, Whitehall Foundation, and NIH grant R01MH132073.

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Authors and Affiliations

  1. Department of Neuroscience, Developmental, and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX, USA

    Kelly Lozano-Ortiz, Ada C. Felix-Ortiz, Jaelyn M. Terrell, Carolina Gonzalez, Kamryn R. Whitehorn, Addison E. Kanke, Stephanie A. Villalon, Angelica R. Ramos, Ashley N. Miller & Anthony Burgos-Robles

  2. Brain Health Consortium, The University of Texas at San Antonio, San Antonio, TX, USA

    Kelly Lozano-Ortiz, Ada C. Felix-Ortiz, Jaelyn M. Terrell, Carolina Gonzalez, Kamryn R. Whitehorn, Addison E. Kanke, Stephanie A. Villalon, Angelica R. Ramos, Ashley N. Miller & Anthony Burgos-Robles

  3. Department of Cellular and Integrative Physiology, The University of Texas Health Science Center, San Antonio, TX, USA

    Ada C. Felix-Ortiz

  4. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA

    Jose Rodriguez-Romaguera

  5. Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA

    Jose Rodriguez-Romaguera

  6. Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA

    Jose Rodriguez-Romaguera

  7. Carolina Institute of Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA

    Jose Rodriguez-Romaguera

Authors
  1. Kelly Lozano-Ortiz
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  2. Ada C. Felix-Ortiz
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  7. Stephanie A. Villalon
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  9. Ashley N. Miller
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  10. Jose Rodriguez-Romaguera
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  11. Anthony Burgos-Robles
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Contributions

Conceptualization: ABR and JRR. Research design: ABR, KLO, and JRR. Validation of methods: ABR, KLO, and ACFO. Animal behavior: KLO, ACFO, JMT, CG, KRW, AEK, ARR, SAV, and ANM. Optogenetics: KLO, ACFO, AEK, and ARR. Drug experiment: ABR., KLO, and ARR. Data analysis: ABR, KLO, and ACFO. Histology: KLO, JMT, CG, KRW, ARR, and ANM. Article preparation: ABR, KLO, and JRR. Project supervision: ABR.

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Correspondence to Jose Rodriguez-Romaguera or Anthony Burgos-Robles.

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Lozano-Ortiz, K., Felix-Ortiz, A.C., Terrell, J.M. et al. The prelimbic prefrontal cortex mediates the development of lasting social avoidance as a consequence of social threat conditioning. Neuropsychopharmacol. 50, 1875–1884 (2025). https://doi.org/10.1038/s41386-025-02073-8

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