Ontogeny of the vagal gut-brain axis

Gut-brain communication is a key component of homeostasis which regulates behaviors such as appetite and reward. Intestinal enteroendocrine cells (EECs) translate nutrient intake into signals which affect sensation and behavior, in part through synapse-like contacts with vagal nodose neurons. This direct neuroepithelial circuit regulates feeding (1-3), yet its genesis and role in higher order behaviors remains unknown. We find that EECs first contact nodose neurons in utero, and these interactions require brain-derived neurotrophic factor (BDNF). We show that BDNF regulates the dynamics of these interactions, which underlie EEC-evoked optogenetic excitation of the circuit. In addition to feeding, we discover that this circuit regulates sociability and inhibitory behavioral control. These studies define the ontogeny of a direct gut-brain circuit responsible for early physiology and behavior.