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bioRxiv · 10.1101/2025.05.01.651736

Ontogeny of the vagal gut-brain axis

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

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 (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.

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Lough, K. J., Knox, J. C., Moy, S. S., King, J. S., Williams, S. E.. 2025-05-07. Ontogeny of the vagal gut-brain axis. https://doi.org/10.1101/2025.05.01.651736

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