The Multilayer Connectome of Caenorhabditis elegans

Abstract

Connectomics has focused primarily on the mapping of synaptic links in the brain; yet it is well established that extrasynaptic volume transmission, especially via monoamines and neuropeptides, is also critical to brain function and occurs primarily outside the synaptic connectome. We have mapped the putative monoamine connections, as well as a subset of neuropeptide connections, in C. elegans based on new and published gene expression data. The monoamine and neuropeptide networks exhibit distinct topological properties, with the monoamine network displaying a highly disassortative star-like structure with a rich-club of interconnected broadcasting hubs, and the neuropeptide network showing a more recurrent, highly clustered topology. Despite the low degree of overlap between the extrasynaptic (or wireless) and synaptic (or wired) connectomes, we find highly significant multilink motifs of interaction, pinpointing locations in the network where aminergic and neuropeptide signalling modulate synaptic activity. Thus, the C. elegans connectome can be mapped as a multiplex network with synaptic, gap junction, and neuromodulator layers representing alternative modes of interaction between neurons. This provides a new topological plan for understanding how aminergic and peptidergic modulation of behaviour is achieved by specific motifs and loci of integration between hard-wired synaptic or junctional circuits and extrasynaptic signals wirelessly broadcast from a small number of modulatory neurons.

Author Summary

Connectomics represents an effort to map brain structure at the level of individual neurons and their synaptic connections. However, neural circuits also depend on other types of signalling between neurons, such as extrasynaptic modulation by monoamines and peptides. Here we present a draft monoamine connectome, along with a partial neuropeptide connectome, for the nematode C. elegans, based on new and published expression data for biosynthetic genes and receptors. We describe the structural properties of these "wireless" networks, including their topological features and modes of interaction with the wired synaptic and gap junction connectomes. This multilayer connectome of C. elegans can serve as a prototype for understanding the multiplex networks comprising larger nervous systems, including the human brain.