Complementary lateral hypothalamic populations resist hunger pressure to balance nutritional and social needs

• Published in: Cell metabolism Vol. 35; no. 3; pp. 456 - 471.e6
• Main Authors: Petzold, Anne, van den Munkhof, Hanna Elin, Figge-Schlensok, Rebecca, Korotkova, Tatiana
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.03.2023; Cell Press
• Subjects: Animals; behaving mice; calcium imaging; chemogenetics; feeding; Hunger - physiology; Hypothalamic Area, Lateral - physiology; in vivo; innate behaviors; leptin; Mice; Neurons - physiology; Neurotensin; optogenetics; social interaction; neurotensin; innate behaviors; optogenetics; chemogenetics; feeding; social interaction; in vivo; calcium imaging; leptin; behaving mice
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2023.02.008

Animals continuously weigh hunger and thirst against competing needs, such as social contact and mating, according to state and opportunity. Yet neuronal mechanisms of sensing and ranking nutritional needs remain poorly understood. Here, combining calcium imaging in freely behaving mice, optogenetics, and chemogenetics, we show that two neuronal populations of the lateral hypothalamus (LH) guide increasingly hungry animals through behavioral choices between nutritional and social rewards. While increased food consumption was marked by increasing inhibition of a leptin receptor-expressing (LepRLH) subpopulation at a fast timescale, LepRLH neurons limited feeding or drinking and promoted social interaction despite hunger or thirst. Conversely, neurotensin-expressing LH neurons preferentially encoded water despite hunger pressure and promoted water seeking, while relegating social needs. Thus, hunger and thirst gate both LH populations in a complementary manner to enable the flexible fulfillment of multiple essential needs. [Display omitted] •Food-elicited inhibition of LepRLH neurons facilitates food intake•Activation of LepRLH cells limits feeding rebound post-acute food restriction•LepRLH neurons limit nutritional needs in favor of sex-specific social interaction•NtsLH neurons relegate hunger and social interaction to promote drinking Animals continuously weigh hunger and thirst against competing needs, such as social contact and mating, according to state and opportunity. Here, Petzold et al. show that leptin receptor-expressing and neurotensin-expressing neurons in the lateral hypothalamus resist immediate nutritional needs and flexibly prioritize competing needs despite hunger or thirst.