Chemogenetic re-activation of a neuronal ensemble in the lateral hypothalamus that is active during activity-based...

A high level of physical activity is common in patients with anorexia nervosa and can exacerbate symptoms and recovery prognosis. The underlying cause is not known but is most likely regulated by the brain and may derive from energy deficit. Numerous brain regions are activated by energy deficit, and here we identify the lateral hypothalamus (LH) as one of those brain regions by mapping and chemogenetically controlling activated neurons in this area in the activity-based anorexia (ABA) mouse model. Our studies employing the Fos-TRAP2 technique revealed an increased number of activated neurons in the LH and in the lateral septum (LS) of female ABA mice compared to ad libitum fed running controls. Re-activation of these ABA-induced neuronal ensembles in the LH, but not LS, increased both feeding and locomotor activity. Additionally, chemogenetic inhibition decreased both behaviours. These findings suggest that the LH (but not the LS) under energy deficit is an important brain region that controls feeding and excessive running activity in the ABA model.