Hypothalamic neuronal activation in non-human primates drives naturalistic goal-directed eating behavior

Maladaptive feeding behavior is the primary cause of modern obesity. While the causal influence of the lateral hypothalamic area (LHA) on eating behavior has been established in rodents, there is currently no primate-based evidence available on naturalistic eating behaviors. We investigated the role of LHA GABAergic (LHA^GABA) neurons in eating using chemogenetics in three macaques. LHA^GABA neuron activation significantly increased naturalistic goal-directed behaviors and food motivation, predominantly for palatable food. Positron emission tomography and magnetic resonance spectroscopy validated chemogenetic activation. Resting-state functional magnetic resonance imaging revealed that the functional connectivity (FC) between the LHA and frontal areas was increased, while the FC between the frontal cortices was decreased after LHA^GABA neuron activation. Thus, our study elucidates the role of LHA^GABA neurons in eating and obesity therapeutics for primates and humans.