Connectomics of extrasynaptic signalling: applications to the nervous system of Caenorhabditis elegans
University of Cambridge
MRC Laboratory of Molecular Biology
Doctor of Philosophy (PhD)
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Bentley, B. (2017). Connectomics of extrasynaptic signalling: applications to the nervous system of Caenorhabditis elegans (Doctoral thesis). https://doi.org/10.17863/CAM.16873
Connectomics – the study of neural connectivity – is primarily concerned with the mapping and characterisation of wired synaptic links; however, it is well established that long-distance chemical signalling via extrasynaptic volume transmission is also critical to brain function. As these interactions are not visible in the physical structure of the nervous system, current approaches to connectomics are unable to capture them. This work addresses the problem of missing extrasynaptic interactions by demonstrating for the first time that whole-animal volume transmission networks can be mapped from gene expression and ligand-receptor interaction data, and analysed as part of the connectome. Complete networks are presented for the monoamine systems of Caenorhabditis elegans, along with a representative sample of selected neuropeptide systems. A network analysis of the synaptic (wired) and extrasynaptic (wireless) connectomes is presented which reveals complex topological properties, including extrasynaptic rich-club organisation with interconnected hubs distinct from those in the synaptic and gap junction networks, and highly significant multilink motifs pinpointing locations in the network where aminergic and neuropeptide signalling is likely to modulate synaptic activity. Thus, the neuronal connectome can be modelled as a multiplex network with synaptic, gap junction, and neuromodulatory layers representing inter-neuronal interactions with different dynamics and polarity. This represents a prototype for understanding how extrasynaptic signalling can be integrated into connectomics research, and provides a novel dataset for the development of multilayer network algorithms.
Connectomics, C. elegans, Volume Transmission, Dopamine, Serotonin, Octopamine, Tyramine, Neuropeptides, Monoamines, Multilayer Networks, Network Analysis, Neural Circuits, Neuromodulation, Connectome, Network Theory, Neural Networks
This work was supported by the Medical Research Council (MRC).
This record's DOI: https://doi.org/10.17863/CAM.16873
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