Morphological, molecular, and functional evidence for a CNS-like oral nerve ring in the sea anemone Nematostella vectensis

Abstract The emergence of centralized nervous systems reflects a major inflection point in evolution, enabling animals to integrate diverse inputs and coordinate complex behaviors. Neural centralization is typically associated with Bilateria, whereas their sister group, Cnidaria (jellyfish, anemones, and corals), has long been thought to rely on diffuse nerve nets mediating simple reflexes. This view, reinforced by limited anatomical and molecular data, has left unresolved whether cnidarians can form localized centers for neural processing, a question sharpened by the growing recognition of their diverse behavioral repertoires. Here we show that the sea anemone Nematostella vectensis possesses an oral nerve ring composed of ganglion-like condensations, a hallmark of centralized organization. These neurons are enriched for excitatory, inhibitory, and modulatory receptors but lack sensory or ciliary markers, yielding a molecular profile most consistent with bilaterian interneurons. Genetic disruption of a conserved inhibitory receptor subunit predominantly expressed in the oral nerve ring delayed the initiation of swallowing in a novel feeding paradigm, demonstrating a potential role in behavioral regulation. Together, these findings provide converging anatomical, molecular, and functional evidence that cnidarians can assemble localized integrative centers, suggesting that key elements of neural centralization predated the cnidarian–bilaterian split. Competing Interest Statement The authors have declared no competing interest. Footnotes This revision includes updated figure arrangements and Supplementary Information.