We leverage optogenetics to show that the BDNF-dependent, direct interactions are essential for EEC-evoked nodose activity.

We next show that this circuit fails to form properly without EEC-derived BDNF. We employ a novel gut-ganglion explant system to show that BDNF is required to form stable interactions between EECs and nodose neurons.

Through microscopy and embryonic transsynaptic tracing, we show that this circuit first forms in utero. This is the earliest known instance of mammalian gut-brain communication.