Single-nucleus transcriptomics reveals cellular signatures of adaptive remodeling in the adult oyster nervous system after the life-history transition

How nervous systems adapt to major life-history transitions remains poorly understood in indirectly developing animals. The Pacific oyster ( Magallana gigas ) undergoes a planktonic-to-sessile transition during metamorphosis, but functional specialization of its adult ganglia remains unresolved. We used single-nucleus RNA sequencing to construct cell-type atlases of the adult cerebral ganglia (CG) and visceral ganglion (VG). Comparative analyses revealed ganglion-associated differences in cellular composition and neuronal transcriptional programs. Differential expression, KEGG enrichment, and AUCell analyses showed that CG neurons were transcriptionally biased toward homeostatic and protective processes, whereas VG neurons showed higher activity of pathways related to signal modulation and effector output. These differences persisted among transcriptionally matched neuronal populations and were associated with distinct transcription factor expression patterns. Serotonergic neurons were primarily identified in the VG, whereas no corresponding population was resolved in the CG. Computational perturbation, gene regulatory network, and pseudotime analyses identified a candidate Gata3–Pitx–Uncx regulatory module associated with the 5-HT program. VG-associated metabolic glial cells also displayed transport, redox, detoxification, and amino acid metabolism-related features. Cell–cell communication, pseudotime, and cross-species cell-type similarity analyses supported their glial-like identity and suggested potential neural-support roles. Adult oyster CG and VG exhibit distinct cellular and molecular specializations. Together with previous studies of the larval apical organ, our findings support a working model in which functional emphasis may shift toward the adult VG after metamorphosis. This model provides a testable framework for investigating nervous system adaptation across life-history transitions and guides future experimental validation.