THE EFFECT OF WHEEL RUNNING ON THE ACTIVITY OF PKC-Δ+ NEURONS IN MICE WITH ACTIVITY-BASED ANOREXIA

Abstract

Anorexia nervosa (AN) is an eating disorder that is characterized by significantly restricted eating, irrational obsession with thinness, and oftentimes over-exercising. However, the neural mechanism underlying anorexia development is still poorly understood and targeted therapy is not available. The purpose of this study is to better understand the effects of physical activity on the neural factors that lead to the development and prognosis of anorexia nervosa. In addition to mediating fear and anxiety responses, the central nucleus of the amygdala (CEA) has been understood to play a role in feeding regulation. Specifically, a subpopulation of GABAergic neurons in the CEA that express protein kinase C-delta (PKC-δ+) are known to mediate diverse anorexigenic signals, and these neurons are required for the development of activity-based anorexia (ABA) in rodents. ABA is a commonly used biobehavioral animal model to mimic anorexia nervosa in humans, in which food-restricted mice run themselves to death if given access to a running wheel. We employed in vivo calcium imaging to study the activity of PKC-δ+ neurons during wheel running over the development of ABA in mice (n=3). We found that wheel running reduces the activity of PKC-δ+ neuron activity in fed, fasted, and ABA mice. Interestingly, when ABA has fully developed, wheel running elicits an even stronger activity reduction in PKC-δ+ neurons. Our data suggest that CEA PKC-δ+ neurons may play a role in mediating satiety signals following bouts of exercise, and that feeding and exercise behaviors are regulated by overlapping neural mechanisms.