Abstract: Efforts are ongoing to build and map synaptic wiring diagrams, or connectomes, to understand the neural basis of brain function. However, chemical synapses represent only one type of functionally important signalling interaction between neurons; in particular, extrasynaptic neuromodulatory interactions involving neuropeptides are widespread in all nervous systems, and these wireless interactions are critical to the function of all animal brains. To probe the structure and function of these networks, we have integrated single-cell anatomical and gene expression datasets with comprehensive biochemical analysis of receptor-ligand interactions to generate a draft neuropeptide connectome for the nematode C. elegans. This network exhibits a high density of connections, extended signaling cascades, autocrine foci, and a decentralised topology. We anticipate that the C. elegans neuropeptidergic connectome will likewise serve as a prototype to understand basic organisational principles of neuroendocrine signaling networks in other animals, including humans.

We have also begun to investigate both wired and wireless connectivity in the complex, „alien“ brain of the octopus. These animals evolved brain complexity independently of vertebrates, and their nervous systems appear to show novel innovations at the molecular and circuit levels. Our ongoing efforts to generate a molecularly-resolved connectome of the octopus hatchling brain will be presented.