A lateral hypothalamic neuronal population expressing leptin receptors counteracts anxiety to enable adaptive behavioral responses

Abstract Neuronal mechanisms that facilitate adaptive strategies to enable an animal to overcome anxiety in threatening situations remain unknown. Using single-cell calcium imaging and cell-type-specific activity manipulations in behaving mice, we identified leptin-sensitive neuronal subpopulations in the lateral hypothalamus (LH; LepR LH ) that encode anxiogenic stimuli. In high-anxiety animals, LepR LH neurons differentiated poorly among anxiogenic stimuli and were inhibited by input from the prefrontal cortex. The activity of LepR LH neurons predicted the anxiety level of individual animals, and the activation of LepR LH neurons enabled adaptive responses under anxiogenic conditions—exploration of new terrain, eating despite anxiogenic environment and limiting maladaptive excessive locomotion in an anorexia nervosa disease model. Thus, leptin-sensitive neuronal subpopulations in the LH enable adaptive fulfillment of vital needs despite anxiogenic conditions, both in healthy and pathological states.