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 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 amygdala and BNST, 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 depolarised by GABA transmission. Together, we established the role of MoV neurons in feeding regulation and advanced the understanding of hindbrain feeding regulation network. Significance Statement Despite the extensive research of hypothalamic feeding regulation neural circuits, the nucleus that controls chewing, trigeminal motor nucleus (MoV), has rarely been considered in literature reviews as part of the feeding circuits, representing a major gap of knowledge in feeding regulation. In this manuscript, we mapped the inputs of MoV neurons using rabies virus method and revealed surprising direct connections with forebrain regions including amygdala. We also examined the functional impact of manipulating MoV neurons, or MoV-projecting CeA neurons, in feeding behavior and confirmed that MoV neurons only fine-tune the microstructure of feeding behavior without influencing total food consumption, suggesting that appetite is controlled by upstream feeding regulation neurons in hypothalamus or other brain regions.