Distinct lateral hypothalamic GABAergic ensembles encode motivational salience and value-scaled consumption

Abstract

Motivated behaviors span an approach-avoidance axis. Vgat-expressing lateral hypothalamic GABAergic neurons (LHVgat neurons) regulate motivated behaviors, but how distinct ensembles represent motivationally significant stimuli and consummatory actions across homeostatic needs remains unclear. Using longitudinal two-photon Ca2+ imaging to track individual neurons across behavioral sessions, we identify two dissociable LHVgat ensembles. One responds to aversive thermal stimuli and food-associated cues, including inaccessible food and learned predictors, but not to a behaviorally neutral auditory tone that evokes pupil dilation, supporting motivational salience coding across aversive and appetitive contexts rather than reflecting arousal alone. A second ensemble is preferentially engaged during ingestion across eating and drinking. Food-cue responses vary across stimuli in a manner consistent with their relative appetitive value, and ingestion responses scale with hunger and nutrient concentration; GLP-1 receptor agonism attenuates both. These findings reveal a functional division between motivationally salient cue processing and value-scaled consummatory encoding in LHVgat circuits.