DISTINCT NEURONAL CELL POPULATIONS IN THE LATERAL HYPOTHALAMUS PROCESSING ANXIETY-RELATED BEHAVIOR

Animals must continuously assess environmental risk to flexibly regulate feeding and other essential behaviors. The lateral hypothalamus (LH) is a key integrative center for motivated behavior, yet the specific neuronal populations that contribute to anxiety-related behavioral adaptation remain incompletely understood.
Here, we investigated the role of leptin receptor–expressing neurons in the LH (LepRLH) in the regulation of anxiety-related behavior. Using cell-type-specific knockdown, as well as opto- and chemogenetic manipulation in freely behaving mice, we examined how activity of LepRLH neurons relate to anxiogenic conditions across different behavioral contexts. Anxiety levels were associated with expression of anorexia nervosa risk genes in LepRLH neurons. In parallel, we assessed the contribution of neurotensin-expressing LH neurons (NtsLH) to anxiety processing.
Our findings support a role for LepRLH neurons in anxiety-related behavioral regulation, whereas NtsLH neurons appear not to be directly involved in this process. Together, these data suggest that distinct LH neuronal populations make dissociable contributions to behavioral adaptation under conditions of perceived threat, highlighting functional specialization within hypothalamic circuits that support flexible responses to environmental challenges.