{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:14:40Z","timestamp":1792250080404,"version":"4.4.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014370","name":"Simons Foundation Autism Research Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014370","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neural Circuits"],"abstract":"<jats:p>Social dominance hierarchies are a common adaptation to group living and exist across a broad range of the animal kingdom. Social dominance is known to rely on the prefrontal cortex (PFC), a brain region that shows a protracted developmental trajectory in mice. However, it is unknown to what extent the social dominance hierarchy is plastic across postnatal development and how it is regulated. Here we identified a sensitive period for experience-dependent social dominance plasticity in adolescent male mice, which is regulated by mechanisms that affect cortical plasticity. We show that social dominance hierarchies in male mice are already formed at weaning and are highly stable into adulthood. However, one experience of forced losing significantly reduces social dominance during the adolescent period but not in adulthood, suggesting adolescence as a sensitive period for experience-dependent social dominance plasticity. Notably, robust adolescent plasticity can be prolonged into adulthood by genetic deletion of <jats:italic>Lynx1<\/jats:italic>, a molecular brake that normally limits cortical plasticity through modulation of cortical nicotinic signaling. This plasticity is associated with increased activation of established nodes of the social dominance network including dorsal medial PFC and medial dorsal thalamus evidenced by increased c-Fos. Pharmacologically mediated elevation of cortical plasticity by valproic acid rapidly destabilizes the hierarchy of adult wildtype animals. These findings provide insight into mechanisms through which increased behavioral plasticity may be achieved to improve therapeutic recovery from psychiatric disorders that are associated with social deficits.<\/jats:p>","DOI":"10.3389\/fncir.2021.676308","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T07:47:23Z","timestamp":1620805643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["An Adolescent Sensitive Period for Social Dominance Hierarchy Plasticity Is Regulated by Cortical Plasticity Modulators in Mice"],"prefix":"10.3389","volume":"15","author":[{"given":"Lucy K.","family":"Bicks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana","family":"Taub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Schahram","family":"Akbarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14964","DOI":"10.1523\/jneurosci.4812-10.2010","article-title":"Removing brakes on adult brain plasticity: from molecular to behavioral interventions.","volume":"30","author":"Bavelier","year":"2010","journal-title":"J. Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.eplepsyres.2007.06.009","article-title":"Valproate selectively reduces EEG activity in anterior parts of the cortex in patients with idiopathic generalized epilepsy: a low resolution electromagnetic tomography (LORETA) study.","volume":"75","author":"B\u00e9la","year":"2007","journal-title":"Epilepsy Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.3389\/fpsyg.2015.01805","article-title":"Prefrontal cortex and social cognition in mouse and man.","volume":"6","author":"Bicks","year":"2015","journal-title":"Front. Psychol."},{"key":"B4","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/s41467-020-14740-z","article-title":"Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior.","volume":"11","author":"Bicks","year":"2020","journal-title":"Nat. Commun."},{"key":"B5","doi-asserted-by":"publisher","first-page":"12693","DOI":"10.1523\/jneurosci.4315-14.2015","article-title":"Unmasking proteolytic activity for adult visual cortex plasticity by the removal of Lynx1.","volume":"35","author":"Bukhari","year":"2015","journal-title":"J. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1124\/pr.111.005512","article-title":"Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder.","volume":"65","author":"Chiu","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1093\/biomet\/74.2.432","article-title":"Ranking from unbalanced paired-comparison data.","volume":"74","author":"David","year":"1987","journal-title":"Biometrika"},{"key":"B8","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.neuron.2007.09.034","article-title":"Gain modulation by nicotine in macaque v1.","volume":"56","author":"Disney","year":"2007","journal-title":"Neuron"},{"key":"B9","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1006\/anbe.2003.2226","article-title":"David\u2019s score: a more appropriate dominance ranking method than Clutton-Brock et al.\u2019s index.","volume":"66","author":"Gammell","year":"2003","journal-title":"Anim. Behav."},{"key":"B10","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3389\/fnsys.2013.00102","article-title":"Valproate reopens critical-period learning of absolute pitch.","volume":"7","author":"Gervain","year":"2013","journal-title":"Front. Syst. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3274","DOI":"10.1523\/jneurosci.16-10-03274.1996","article-title":"Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse.","volume":"16","author":"Gordon","year":"1996","journal-title":"J. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1146\/annurev.neuro.27.070203.144327","article-title":"Critical period regulation.","volume":"27","author":"Hensch","year":"2004","journal-title":"Annu. Rev. Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/s0896-6273(02)00632-3","article-title":"Novel modulation of neuronal nicotinic acetylcholine receptors by association with the endogenous prototoxin lynx1.","volume":"33","author":"Iba\u00f1ez-Tallon","year":"2002","journal-title":"Neuron"},{"key":"B14","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.cell.2019.05.022","article-title":"Correlated neural activity and encoding of behavior across brains of socially interacting animals.","volume":"178","author":"Kingsbury","year":"2019","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/191474a0","article-title":"Social dominance in inbred mouse strains.","volume":"191","author":"Lindzey","year":"1961","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1111\/j.1755-5949.2010.00203.x","article-title":"Histone deacetylases and mood disorders: epigenetic programming in gene-environment interactions.","volume":"17","author":"Machado-Vieira","year":"2011","journal-title":"CNS Neurosci. Ther."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1126\/science.1220845","article-title":"A critical period for social experience-dependent oligodendrocyte maturation and myelination.","volume":"337","author":"Makinodan","year":"2012","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1126\/science.1150516","article-title":"The antidepressant fluoxetine restores plasticity in the adult visual cortex.","volume":"320","author":"Maya Vetencourt","year":"2008","journal-title":"Science"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.1126\/science.1114362","article-title":"Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor.","volume":"309","author":"McGee","year":"2005","journal-title":"Science"},{"key":"B20","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/s0896-6273(00)80757-6","article-title":"lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine receptors in the mammalian CNS.","volume":"23","author":"Miwa","year":"1999","journal-title":"Neuron"},{"key":"B21","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.neuron.2006.07.025","article-title":"The prototoxin lynx1 acts on nicotinic acetylcholine receptors to balance neuronal activity and survival in vivo.","volume":"51","author":"Miwa","year":"2006","journal-title":"Neuron"},{"key":"B22","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41386-020-00821-6","article-title":"A prefrontal social circuit vulnerable to juvenile social isolation.","volume":"46","author":"Morishita","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.conb.2008.05.009","article-title":"Critical period revisited: impact on vision.","volume":"18","author":"Morishita","year":"2008","journal-title":"Curr. Opin. Neurobiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1126\/science.1195320","article-title":"Lynx1, a cholinergic brake, limits plasticity in adult visual cortex.","volume":"330","author":"Morishita","year":"2010","journal-title":"Science"},{"key":"B25","article-title":"Molecular and circuit architecture of social hierarchy.","author":"Nelson","year":"2019","journal-title":"bioRxiv"},{"key":"B26","doi-asserted-by":"publisher","first-page":"36734","DOI":"10.1074\/jbc.m101287200","article-title":"Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen.","volume":"276","author":"Phiel","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1126\/science.1072699","article-title":"Reactivation of ocular dominance plasticity in the adult visual cortex.","volume":"298","author":"Pizzorusso","year":"2002","journal-title":"Science"},{"key":"B28","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.neuron.2007.02.007","article-title":"Developmental downregulation of histone posttranslational modifications regulates visual cortical plasticity.","volume":"53","author":"Putignano","year":"2007","journal-title":"Neuron"},{"key":"B29","doi-asserted-by":"publisher","first-page":"9472","DOI":"10.1523\/jneurosci.0580-16.2016","article-title":"Lynx1 limits dendritic spine turnover in the adult visual cortex.","volume":"36","author":"Sajo","year":"2016","journal-title":"J. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1111\/j.1460-9568.2010.07261.x","article-title":"Epigenetic treatments of adult rats promote recovery from visual acuity deficits induced by long-term monocular deprivation.","volume":"31","author":"Silingardi","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1126\/science.1128232","article-title":"PirB restricts ocular-dominance plasticity in visual cortex.","volume":"313","author":"Syken","year":"2006","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41593-017-0064-2","article-title":"Inhibitory circuit gating of auditory critical-period plasticity.","volume":"21","author":"Takesian","year":"2018","journal-title":"Nat. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1016\/j.psyneuen.2010.05.011","article-title":"A role for glucocorticoids in the long-term establishment of a social hierarchy.","volume":"35","author":"Timmer","year":"2010","journal-title":"Psychoneuroendocrinology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1038\/npp.2014.319","article-title":"Sex-Specific mechanism of social hierarchy in mice.","volume":"40","author":"van den Berg","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.tins.2014.07.005","article-title":"The mouse that roared: neural mechanisms of social hierarchy.","volume":"37","author":"Wang","year":"2014","journal-title":"Trends Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1126\/science.1209951","article-title":"Bidirectional control of social hierarchy by synaptic efficacy in medial prefrontal cortex.","volume":"334","author":"Wang","year":"2011","journal-title":"Science"},{"key":"B37","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1080\/17470919.2018.1479303","article-title":"Immediate early gene activation throughout the brain is associated with dynamic changes in social context.","volume":"14","author":"Williamson","year":"2019","journal-title":"Soc. Neurosci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.anbehav.2016.03.004","article-title":"Temporal dynamics of social hierarchy formation and maintenance in male mice.","volume":"115","author":"Williamson","year":"2016","journal-title":"Anim. Behav."},{"key":"B39","first-page":"324","article-title":"The roles of dopamine D1 receptor on the social hierarchy of rodents and nonhuman primates.","volume":"20","author":"Yamaguchi","year":"","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B40","doi-asserted-by":"crossref","first-page":"43348","DOI":"10.1038\/srep43348","article-title":"The roles of dopamine D2 receptor in the social hierarchy of rodents and primates.","volume":"7","author":"Yamaguchi","year":"","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1038\/s41593-020-0695-6","article-title":"A prefrontal-paraventricular thalamus circuit requires juvenile social experience to regulate adult sociability in mice.","volume":"23","author":"Yamamuro","year":"2020","journal-title":"Nat. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"17213","DOI":"10.1073\/pnas.1200705109","article-title":"Critical period for acoustic preference in mice.","volume":"109","author":"Yang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B43","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.conb.2018.01.006","article-title":"Advances in understanding neural mechanisms of social dominance.","volume":"49","author":"Zhou","year":"2018","journal-title":"Curr. Opin. Neurobiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1126\/science.aak9726","article-title":"History of winning remodels thalamo-PFC circuit to reinforce social dominance.","volume":"357","author":"Zhou","year":"2017","journal-title":"Science"}],"container-title":["Frontiers in Neural Circuits"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2021.676308\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T07:47:33Z","timestamp":1620805653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2021.676308\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":44,"alternative-id":["10.3389\/fncir.2021.676308"],"URL":"https:\/\/doi.org\/10.3389\/fncir.2021.676308","relation":{},"ISSN":["1662-5110"],"issn-type":[{"value":"1662-5110","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]},"article-number":"676308"}}