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dc.contributor.authorBentley, Barry
dc.date.accessioned2017-12-07T14:34:52Z
dc.date.available2017-12-07T14:34:52Z
dc.date.issued2017-12-04
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/270033
dc.description.abstractConnectomics – 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.
dc.description.sponsorshipThis work was supported by the Medical Research Council (MRC).
dc.language.isoen
dc.rightsAll Rights Reserveden
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/en
dc.subjectConnectomics
dc.subjectC. elegans
dc.subjectVolume Transmission
dc.subjectDopamine
dc.subjectSerotonin
dc.subjectOctopamine
dc.subjectTyramine
dc.subjectNeuropeptides
dc.subjectMonoamines
dc.subjectMultilayer Networks
dc.subjectNetwork Analysis
dc.subjectNeural Circuits
dc.subjectNeuromodulation
dc.subjectConnectome
dc.subjectNetwork Theory
dc.subjectNeural Networks
dc.titleConnectomics of extrasynaptic signalling: applications to the nervous system of Caenorhabditis elegans
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.publisher.departmentMRC Laboratory of Molecular Biology
dc.date.updated2017-12-07T14:17:41Z
dc.identifier.doi10.17863/CAM.16873
dc.contributor.orcidBentley, Barry [0000-0002-4360-5902]
dc.publisher.collegeMagdalene College
dc.type.qualificationtitleBiological Science
cam.supervisorSchafer, William R.
cam.supervisor.orcidSchafer, William R. [0000-0002-6676-8034]
rioxxterms.freetoread.startdate2017-12-07


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