6.131 NEURODEVELOPMENT OF PARVALBUMIN CELLS AND PERINEURONAL NETS FOLLOWING EARLY LIFE TRAUMA

• Published in: Journal of the American Academy of Child and Adolescent Psychiatry Vol. 55; no. 10; p. S246
• Main Authors: Santiago, Adrienne N., BA, Lim, Kayla Y, Sullivan, Regina M., PhD, Aoki, Chiye, PhD
• Format: Journal Article
• Language: English
• Published: Baltimore Elsevier Inc 01.10.2016; Elsevier BV
• Subjects: Abuse; Amygdala; Bedding; Behavior; Caregivers; Cells; Child & adolescent psychiatry; Correlation analysis; Critical period; Developmental stages; Dissolution; Fear & phobias; Immunohistochemistry; Interneurons; Jumping; Maturation; Mental disorders; Mental health care; Nets; Parvalbumin; Pediatrics; Perineuronal nets; Psychiatry; Responsiveness; Severity; Social development; Therapeutic applications; Trauma; Vulnerability; Weaning; Young Children
• ISSN: 0890-8567; 1527-5418
• DOI: 10.1016/j.jaac.2016.09.447

Objectives: Early life trauma, particularly during the developmental sensitive period for infant attachment, is a major risk factor for later-life vulnerability to psychiatric disorders characterized by heightened fearfulness. The basolateral amygdala (BLA), long known for its integral role in threat response behavior, has recently been shown to be hyper-responsive in juveniles following early life abuse from the caregiver. However, the anatomical substrates that mediate increased responsiveness of the BLA at a synaptic level are unknown. Fast-spiking parvalbumin positive (PV+) inhibitory interneurons are known to play a major role in defining critical periods of neurodevelopment and have been shown to play a critical role in BLA fear response. A class of extracellular molecules referred to as perineuronal nets (PNNs), have been shown to end critical periods of neurodevelopment by locking axo-somatic synapses onto PV+ somata. Our objective is to establish whether early life abuse affects PV+ cell and PNN maturation, and whether dissolution of PNNs during healthy maternal care will correct abnormal threat response behavior in abused pups. Methods: We use a rat model of early life abuse in which the mother rat is given insufficient bedding with which to make her nest. The mother exhibits rough handling and frequent stepping or jumping on her infant pups. Abused rat pups exhibit abnormal behavioral threat responses which are associated with increased activity in the BLA. Here, we use immunohistochemistry to characterize PNN and PV cell development over three specific pre-weaning time points: PN 15, PN18, and PN23. We then tested the effects of enzyme dissolution of the PNNs on neural development and threat response behavior. Results: We report group differences at all three developmental time points, as well as correlational data between PV and PNN prevalence and threat response behavior. We also report correlations between severity of abuse and PNN development. Finally, we present preliminary data reporting the effects of PNN dissolution on threat response behavior. Conclusions: Here we identify PV+ cells and the PNNs that encapsulate them as a potential therapeutic target for reversing the effects of early life trauma before they manifest at weaning.