No abstract

Anorexia nervosa (AN) is a serious psychiatric disease characterized by restricted eating, fear of gaining weight, as well as excessive exercise, and also is often comorbid with emotional disorders such as anxiety and depression. However, the etiology of AN is unknown and the neural mechanism that leads to AN remains to be determined. Here, we show that a specific subpopulation of neurons, marked by the expression of protein kinase C-delta (PKC-δ), in two nuclei of the central extended amygdala (EAc)— central nucleus (CeA) and oval region of bed nucleus of stria terminalis (ovBNST)—regulates development of activity-based anorexia (ABA), the current best animal model of AN. Specifically, simultaneous dual ablation of CeAPKC-δand ovBNSTPKC-δneurons prevents the key phenotypes of ABA: increases in wheel activity, decreases in food intake, and life-threatening body weight loss. However, ablating PKC-δ neurons in CeA or ovBNST alone is not sufficient to prevent ABA. Correspondingly, activation of PKC-δ neurons in one type of nuclei continues to suppress food intake even when PKC-δ neurons in the other nuclei are silenced. Consistent with their role in suppressing food intake when activated, these PKC-δ neurons show increased activity with ABA development. Together, our study illuminates how neurons in the amygdala regulate ABA development and supports the complex and heterogenous etiology of AN.