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J Comp Neurol. 2018 Nov 1;526(16):2647-2664. doi: 10.1002/cne.24522. Epub 2018 Oct 18.

Early life trauma increases threat response of peri-weaning rats, reduction of axo-somatic synapses formed by parvalbumin cells and perineuronal net in the basolateral nucleus of amygdala.

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Center for Neural Science, New York University, New York, New York.
Emotional Brain Institute, Nathan Kline Institute, New York University School of Medicine, New York, New York.
Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, New York.


Early life trauma is a risk factor for life-long disorders related to emotional processing, but knowledge underlying its enduring effect is incomplete. This study was motivated by the hypothesis that early life trauma increases amygdala-dependent threat responses via reduction in inhibition by parvalbumin (PV) interneurons and perineuronal nets (PNN) supporting PV cells, thus increasing excitability of the basolateral amygdala (BLA). From postnatal day (PN) 8-12, rat pups of both sexes were reared under normal bedding or under insufficient nest-building materials to induce maternal-to-infant maltreatment trauma (Scarcity-Adversity Model, SAM). At weaning age of PN23, the SAM group exhibited increased threat responses to predator odor. The SAM-induced increase in threat response was recapitulated in normally reared PN22-23 rats that were unilaterally depleted of PNN in the BLA by the enzymes, chondroitinase-ABC plus hyaluronidase at PN19-20. Light and electron microscopic analysis of the BLA revealed that anterior-to-mid levels of SAM group's BLAs exhibited decreased PNN intensity and decreased axo-somatic synapses between PV-to-principal pyramidal-like neurons and PV-to-PV. PV and PNN densities (cells/mm2 ) in the BLA of both control (CON) and SAM groups were still low at PN12 and SAM delayed the ontogenetic rise of PV intensity and PNN density. Moreover, PV cell density in the anterior-to-mid BLA correlated negatively with threat response of CON animals, but not for SAM animals. Thus, reduction of PNN-supported, PV-mediated somatic inhibition of pyramidal cells provides a mechanistic support for the enduring effect of early life maltreatment manifested as increasing innate threat response at weaning.


PNN; RRID: AB_477329; amygdala; infant maltreatment; innate fear; parvalbumin; perineuronal net; predator odor


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