Molecular Neurobiology of Loss

• DOI: 10.1101/2022.07.13.499899
• Publication Date: 2022-07-14T03:30:10Z
• Authors: Marissa A. Smail; Brittany L. Smith; Rammohan Shukla; Khaled Alganem; Hunter M. Eby; Justin L. Bollinger; Ria K. Parikh; James B. Chambers; James K. Reigle; Rachel D. Moloney; Nawshaba Nawreen; Eric S. Wohleb; Harry Pantazopoulos; Robert E. McCullu...; James P. Herman
• Keywords: Perineuronal net; Basolateral amygdala

ABSTRACT Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings are poorly understood. Here, we investigate the mechanisms using an enrichment removal (ER) paradigm in rats. A comprehensive multi-omics investigation basolateral amygdala (BLA) revealed alterations microglia extracellular matrix (ECM). Follow-up studies indicated ER decreased size, complexity, phagocytosis, suggesting reduced immune surveillance. Loss also substantially increased ECM coverage, specifically targeting perineuronal nets surrounding parvalbumin interneurons, plasticity inhibition BLA following loss. Behavioral analyses suggest these effects linked to impaired salience evaluation, reflecting emotional blunting observed human These loss-like behaviors could be rescued by depleting during removal, helping us understand underlying revealing novel targets ameliorate its impact.