Lough, K. J.; Knox, J. C.; Moy, S. S.; King, J. S.; Williams, S. E.

Gut-brain communication is a key component of homeostasis which regulates behaviors such as appetite and reward. Intestinal entero-endocrine 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, 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.