Trigeminal Motor Nucleus Regulates Microstructure of Feeding Behavior without Affecting Total Food Intake

Feeding is critical for animal survival and is tightly regulated by designated neural circuits. Several brain regions have been implicated in feeding regulation, including the hypothalamus, amygdala, parabrachial nucleus, and others. However, how these feeding regulation neurons communicate with the executors of feeding behavior, the trigeminal motor (MoV) neurons that directly control mastication muscles, is unclear. Despite its clear involvement in feeding, MoV is rarely considered as a part of the feeding neural network in literature reviews, indicating an incomplete conceptual framework of feeding regulation. Here, by using Isl1 and ChAT as neuronal markers, we genetically targeted MoV neurons to reveal its connections with other brain regions and investigated their function in feeding in mice of either sex. Notably, we identified direct connection of MoV neurons with forebrain regions including the amygdala and bed nucleus of the stria terminalis, while hypothalamic feeding regulation neurons do not represent as a major direct regulator of MoV neurons. Functionally, although complete silencing of MoV neurons renders the mice incapable of eating, acute inhibition or activation of MoV neurons only changed microstructure of feeding behavior without influencing total food intake, suggesting that MoV neurons mainly function as the executor of feeding but are not involved in appetite regulation. Moreover, activating the GABAergic input neurons of MoV neurons generated similar effect as activating the MoV neurons, because MoV neurons are depolarized by GABA transmission. Together, we established the role of MoV neurons in feeding regulation and advanced the understanding of hindbrain feeding regulation network.