LEPTIN-SENSITIVE NEURONS IN LATERAL HYPOTHALAMUS COUNTERACT ANXIETY TO ENABLE ADAPTIVE BEHAVIORAL RESPONSES UNDER ANXIOGENIC CONDITIONS AND IN AN ANOREXIA NERVOSA MOUSE MODEL

Neuronal mechanisms that facilitate adaptive strategies and enable an animal to overcome anxiety in threatening situations are largely unknown. Using single-cell calcium imaging, optogenetics and chemogenetics in behaving male and female mice, we identified leptin-sensitive neuronal subpopulations in the lateral hypothalamus (LepR^LH) that encode anxiogenic stimuli.
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 the activity-based anorexia nervosa mouse model. During stimulation of inputs from prefrontal cortex to LH, the inhibition of LepR^LH neurons was positively correlated with anxiety levels. Activity of LepR^LH neurons predicted the anxiety level of individual animals, and in high-anxiety animals LepR^LH neurons differentiated poorly between anxiogenic stimuli. Further, activity of LepR^LH neurons encoded stages of anorexia nervosa disease model.
When environmental or internal conditions change, regulation of LepR^LH neurons may extend beyond feeding to include other behaviors, such as social interaction.Taken together, leptin-sensitive neuronal subpopulations in the LH enable adaptive fulfillment of vital needs despite anxiogenic conditions, both in health and in anorexia nervosa disease model.
We gratefully acknowledge support by the ERC consolidator grant HypFeedNet (to TK), DFG RTG1960 (to RF), DFG CRC1451 (to TK and AP), EXC2030-CECAD to T.K.