title: Enduring good memories of infant trauma: rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction.
abstract: Children form a strong attachment to their caregiver--even when that caretaker is abusive. Paradoxically, despite the trauma experienced within this relationship, the child develops a preference for trauma-linked cues--a phenomenon known as trauma bonding. Although infant trauma compromises neurobehavioral development, the mechanisms underlying the interaction between infant trauma bonding (i.e., learned preference for trauma cues) and the long-term effects of trauma (i.e., depressive-like behavior, amygdala dysfunction) are unknown. We modeled infant trauma bonding by using odor-shock conditioning in rat pups, which engages the attachment system and produces a life-long preference for the odor that was paired with shock. In adulthood, this trauma-linked odor rescues depressive-like behavior and amygdala dysfunction, reduces corticosterone (CORT) levels, and exerts repair-related changes at the molecular level. Amygdala microarray after rescue implicates serotonin (5-HT) and glucocorticoids (GCs), and a causal role was verified through microinfusions. Blocking amygdala 5-HT eliminates the rescue effect; increasing amygdala 5-HT and blocking systemic CORT mimics it. Our findings suggest that infant trauma cues share properties with antidepressants and safety signals and provide insight into mechanisms by which infant trauma memories remain powerful throughout life.
authors.affiliation: Emotional Brain Institute, Nathan Kline Institute, Orangeburg, NY 10962; Neuroscience and Physiology, Sackler Institute, New York University School of Medicine, New York, NY 10016; Child and Adolescent Psychiatry, The Child Study Center, New York University Langone Medical Center, NY 10016; millie.rinconcortes@med.nyu.edu regina.sullivan@nyumc.org.
authors.forename: Millie
authors.identifier: http://orcid.org/0000-0003-2689-915X
authors.initials: M
authors.lastname: Rincón-Cortés
authors.affiliation: Anesthesia and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Barr
authors.affiliation: Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, University Lyon1, F-69366 Lyon, France; and.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Mouly
authors.affiliation: Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping 58183, Sweden.
authors.forename: Kiseko
authors.initials: K
authors.lastname: Shionoya
authors.affiliation: Emotional Brain Institute, Nathan Kline Institute, Orangeburg, NY 10962;
authors.forename: Bestina S
authors.initials: BS
authors.lastname: Nuñez
authors.affiliation: Emotional Brain Institute, Nathan Kline Institute, Orangeburg, NY 10962; Neuroscience and Physiology, Sackler Institute, New York University School of Medicine, New York, NY 10016; Child and Adolescent Psychiatry, The Child Study Center, New York University Langone Medical Center, NY 10016; millie.rinconcortes@med.nyu.edu regina.sullivan@nyumc.org.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Sullivan
mesh_terms: D000328:Adult; D000679:Amygdala / Q000378:metabolism / Q000503:physiopathology*; D001519:Behavior; D003345:Corticosterone / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008568:Memory; D012701:Serotonin / Q000378:metabolism*; D014947:Wounds and Injuries / Q000523:psychology*
chemical_list: D012701:Serotonin; D003345:Corticosterone
keywords: amygdala; depression; infant trauma; safety signal; serotonin