Neural Mechanism of Hunger-gated Food-seeking and Evaluating

The physiological need for energy evokes motivated feeding behaviours that help to ensure survival. However, the neural mechanisms underlying the generation of food motivation remain poorly understood. We investigated these mechanisms by subdividing feeding-related motivated behaviours into food-seeking, evaluating, and swallowing. Micro-endoscopic results indicated that neurons containing leptin receptors (LepRs) in the lateral hypothalamus (LH) are the major food-specific subpopulation of LH GABA neurons. Optogenetic manipulation of LH LepR neurons bidirectionally regulated both food-seeking and evaluating. Furthermore, micro-endoscope data revealed that distinct LH LepR neurons encode seeking and evaluating. Computational modelling analysis demonstrated that LH LepR neurons encode motivation, whereas neurons containing agouti-related peptide and neuropeptide Y (AgRP/NPY) encode the need for food. Additionally, slice studies revealed that NPY decreases inhibitory input to LH LepR neurons via LH GABA interneurons. This mechanism explains the permissive gate role of hunger (food need) in seeking/evaluating motivation. Together, the present study provides a comprehensive neural mechanism of how physiological needs drive distinct motivated behaviours.