Neurons, Muscles, and Venom: Identifying Drivers of Cephalopod Predation

Coleoid cephalopods (octopuses, squids, and cuttlefish) produce venoms in their posterior salivary glands. Despite venom’s importance in cephalopod evolution and ecology, its regulation and secretion processes remain unresolved. Here, we performed multimodal histological profiling and live imaging to map the glandular architecture and innervation patterns across multiple coleoid species. Micro-computed tomography and tetrachrome alongside hematoxylin and eosin stains verified the proposed differentiation of gland tubular structures into (i) secretory tubules - for venom production - and (ii) striated tubules - potentially propelling venom towards the salivary duct. By tracing five neuronal markers, including nicotine acetylcholine receptors and synapsin, we observed dense neural networks intimately associated with localized muscular signals surrounding the tubules. These findings reveal a spatially distinct organization of venom production and release sites and strongly indicating that neuromuscular signals coordinate venom release into the salivary duct. Although the precise neural circuitry remains to be mapped, our results offer novel understanding of venom gland regulation in marine venomous invertebrates.