Organization of neuropeptide signaling: cross-species insights from small model organisms

Neuropeptides are ancient signaling molecules that modulate neural circuit function and behavior across the animal kingdom. Model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and zebrafish serve as powerful in vivo models for deciphering the organization of neuropeptidergic signaling, owing to their smaller nervous systems, genetic tractability, and the growing availability of neural connectomes. In this article, we review how these organisms have advanced current understanding of neuropeptidergic transmission across three interconnected themes: (i) the roles of peptides in sensory-motor transformations, (ii) the conservation and divergence of peptidergic expression and network architecture across species, and (iii) the diversity of neurotransmission strategies employed by single neurons. Finally, we highlight recent technological innovations as well as open questions that could shape this field in the coming years.