JungMin Kim's research while affiliated with The University of Arizona and other places

Anorexia nervosa (AN) is a serious psychiatric disease, but the neural mechanisms underlying its development are unclear. A subpopulation of amygdala neurons, marked by expression of protein kinase C-delta (PKC-δ), has previously been shown to regulate diverse anorexigenic signals. Here, we demonstrate that these neurons regulate development of activity-based anorexia (ABA), a common animal model for AN. PKC-δ neurons are located in two nuclei of the central extended amygdala (EAc): the central nucleus (CeA) and oval region of the bed nucleus of the stria terminalis (ovBNST). Simultaneous ablation of CeAPKC-δ and ovBNSTPKC-δ neurons prevents ABA, but ablating PKC-δ neurons in the CeA or ovBNST alone is not sufficient. Correspondingly, PKC-δ neurons in both nuclei show increased activity with ABA development. Our study shows how neurons in the amygdala regulate ABA by impacting both feeding and wheel activity behaviors and support a complex heterogeneous etiology of AN.

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 CeA PKC-δ and ovBNST PKC-δ neurons 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.

Loss of appetite or anorexia associated with inflammation impairs quality of life and increases morbidity in many diseases. However, the exact neural mechanism that mediates inflammation-associated anorexia is still poorly understood. Here we identified a population of neurons, marked by the expression of protein kinase C-delta, in the oval region of the bed nucleus of the stria terminalis (BNST), which are activated by various inflammatory signals. Silencing of these neurons attenuates the anorexia caused by these inflammatory signals. Our results demonstrate that these neurons mediate bidirectional control of general feeding behaviors. These neurons inhibit the lateral hypothalamus-projecting neurons in the ventrolateral part of BNST to regulate feeding, receive inputs from the canonical feeding regions of arcuate nucleus and parabrachial nucleus. Our data therefore define a BNST microcircuit that might coordinate canonical feeding centers to regulate food intake, which could offer therapeutic targets for feeding-related diseases such as anorexia and obesity.