Citation

Raineki C, Opendak M, Sarro E, Showler A, Bui K, McEwen BS, Wilson DA, Sullivan RM. Proc. Natl. Acad. Sci. U. S. A. 2019; ePub(ePub): ePub.

Affiliation

Center for Neural Science, New York University, New York, NY 10003.

Copyright

(Copyright © 2019, National Academy of Sciences)

DOI

10.1073/pnas.1907170116

PMID

31636210

Abstract

Infant maltreatment increases vulnerability to physical and mental disorders, yet specific mechanisms embedded within this complex infant experience that induce this vulnerability remain elusive. To define critical features of maltreatment-induced vulnerability, rat pups were reared from postnatal day 8 (PN8) with a maltreating mother, which produced amygdala and hippocampal deficits and decreased social behavior at PN13. Next, we deconstructed the maltreatment experience to reveal sufficient and necessary conditions to induce this phenotype. Social behavior and amygdala deficits (volume, neurogenesis, c-Fos, local field potential) required combined chronic high corticosterone and maternal presence (not maternal behavior). Hippocampal deficits were induced by chronic high corticosterone regardless of social context. Causation was shown by blocking corticosterone during maltreatment and suppressing amygdala activity during social behavior testing. These results highlight (1) that early life maltreatment initiates multiple pathways to pathology, each with distinct causal mechanisms and outcomes, and (2) the importance of social presence on brain development.

Language: en

Keywords

amygdala; corticosterone; hippocampus; maltreatment; social behavior