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.

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References 88

1. 1.

   Bullmore E, Sporns O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nature reviews Neuroscience. 2009;10(3):186–98. Epub 2009/02/05.

   Not in our library10.1038/nrn2575

2. 2.

   White J, Southgate E, Thomson J, Brenner S. The structure of the nervous system of the nematode Caenorhabditis elegans Phil Trans R Soc Lond (Biol). 1986;314:1–340.

   Not in our library10.1098/rstb.1986.0056

3. 3.

   Albertson DG, Thomson JN. The pharynx of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci. 1976;275:299–325.

   Not in our library10.1098/rstb.1976.0085

4. 4.
   Graph theoretical analysis of complex networks in the brain · 2007

   No notice
5. 5.
   Structural Properties of the Caenorhabditis elegans Neuronal Network · 2011

   No notice
6. 6.

   Watts DJ, Strogatz SH. Collective dynamics of 'small-world' networks. Nature. 1998;393(6684):440–2. Epub 1998/06/12.

   Not in our library10.1038/30918

7. 7.
   Network ‘Small-World-Ness’: A Quantitative Method for Determining Canonical Network Equivalence · 2008

   No notice
8. 8.

   Barabasi AL, Albert R. Emergence of scaling in random networks. Science. 1999;286(5439):509–12. Epub 1999/10/16.

   Not in our library10.1126/science.286.5439.509

9. 9.

   Bullmore E, Sporns O. The economy of brain network organization. Nature reviews Neuroscience. 2012;13(5):336–49. Epub 2012/04/14.

   Not in our library10.1038/nrn3214

10. 10.
    Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development · 2014

    No notice
11. 11.

    Towlson EK, Vertes PE, Ahnert SE, Schafer WR, Bullmore ET. The rich club of the C. elegans neuronal connectome. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2013;33(15):6380–7. Epub 2013/04/12.

    Not in our library10.1523/jneurosci.3784-12.2013

12. 12.

    Bargmann CI. Beyond the connectome: how neuromodulators shape neural circuits. BioEssays: news and reviews in molecular, cellular and developmental biology. 2012;34(6):458–65. Epub 2012/03/08.

    Not in our library10.1002/bies.201100185

13. 13.

    Marder E. Neuromodulation of neuronal circuits: back to the future. Neuron. 2012;76(1):1–11. Epub 2012/10/09. PubMed Central PMCID: PMC3482119.

    Not in our library10.1016/j.neuron.2012.09.010

14. 14.

    Brezina V. Beyond the wiring diagram: signalling through complex neuromodulator networks. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 2010;365(1551):2363–74. Epub 2010/07/07. PubMed Central PMCID: PMC2894954.

    Not in our library10.1098/rstb.2010.0105

15. 15.

    Walker RJ, Brooks HL, Holden-Dye L. Evolution and overview of classical transmitter molecules and their receptors. Parasitology. 1996;113 Suppl:S3–33. Epub 1996/01/01.

    Not in our library10.1017/s0031182000077878

16. 16.

    Chase DL, Koelle MR. Biogenic amine neurotransmitters in C. elegans. WormBook: the online review of C elegans biology. 2007:1–15. Epub 2007/12/01.

    Not in our library10.1895/wormbook.1.132.1

17. 17.

    Lin Z, Canales JJ, Bjorgvinsson T, Thomsen M, Qu H, Liu QR, et al Monoamine transporters: vulnerable and vital doorkeepers. Prog Mol Biol Transl Sci. 2011;98:1–46. Epub 2011/01/05. 21199769; PubMed Central PMCID: PMC3321928.

    Not in our library10.1016/b978-0-12-385506-0.00001-6

18. 18.

    Li C, Kim K. Neuropeptides. WormBook: the online review of C elegans biology. 2008:1–36. Epub 2008/09/27. PubMed Central PMCID: PMC2749236.

    Not in our library10.1895/wormbook.1.142.1

19. 19.

    Hobert O. The neuronal genome of Caenorhabditis elegans. WormBook: the online review of C elegans biology. 2013:1–106. Epub 2013/10/02.

    Not in our library10.1895/wormbook.1.161.1

20. 20.

    Ringstad N, Abe N, Horvitz HR. Ligand-gated chloride channels are receptors for biogenic amines in C. elegans. Science. 2009;325(5936):96–100. Epub 2009/07/04. PubMed Central PMCID: PMC2963310.

    Not in our library10.1126/science.1169243

21. 21.

    Chase DL, Koelle MR. Genetic analysis of RGS protein function in Caenorhabditis elegans. Methods in enzymology. 2004;389:305–20. Epub 2004/08/18.

    Not in our library10.1016/s0076-6879(04)89018-9

22. 22.

    Gurel G, Gustafson MA, Pepper JS, Horvitz HR, Koelle MR. Receptors and other signaling proteins required for serotonin control of locomotion in Caenorhabditis elegans. Genetics. 2012;192(4):1359–71. Epub 2012/10/02. PubMed Central PMCID: PMC3512144.

    Not in our library10.1534/genetics.112.142125

23. 23.

    Jafari G, Xie Y, Kullyev A, Liang B, Sze JY. Regulation of extrasynaptic 5-HT by serotonin reuptake transporter function in 5-HT-absorbing neurons underscores adaptation behavior in Caenorhabditis elegans. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2011;31(24):8948–57. Epub 2011/06/17. PubMed Central PMCID: PMC3153855.

    Not in our library10.1523/jneurosci.1692-11.2011

24. 24.

    Duerr JS, Frisby DL, Gaskin J, Duke A, Asermely K, Huddleston D, et al The cat-1 gene of Caenorhabditis elegans encodes a vesicular monoamine transporter required for specific monoamine-dependent behaviors. J Neurosci. 1999;19:72–84.

    Not in our library10.1523/jneurosci.19-01-00072.1999

25. 25.

    Pocock R, Hobert O. Hypoxia activates a latent circuit for processing gustatory information in C. elegans. Nature neuroscience. 2010;13(5):610–4. Epub 2010/04/20. PubMed Central PMCID: PMC3733994.

    Not in our library10.1038/nn.2537

26. 26.

    Nicosia V, Latora V. Measuring and modeling correlations in multiplex networks. Physical review E, Statistical, nonlinear, and soft matter physics. 2015;92(3):032805 Epub 2015/10/16.

    Not in our library10.1103/physreve.92.032805

27. 27.

    Ezcurra M, Tanizawa Y, Swoboda P, Schafer WR. Food sensitizes C. elegans avoidance behaviours through acute dopamine signalling. The EMBO journal. 2011;30(6):1110–22. Epub 2011/02/10. PubMed Central PMCID: PMC3061029.

    Not in our library10.1038/emboj.2011.22

28. 28.

    De Domenico M, Nicosia V, Arenas A, Latora V. Structural reducibility of multilayer networks. Nature communications. 2015;6:6864 Epub 2015/04/24.

    Not in our library10.1038/ncomms7864

29. 29.

    Sorrentino F, di Bernardo M, Cuellar GH, Boccaletti S. Synchronization in weighted scale-free networks with degree-degree correlation. Physica D-Nonlinear Phenomena. 2006;224(1–2):123–9.

    Not in our library

30. 30.
    Evolutionary dynamics of group interactions on structured populations: a review · 2013

    No notice
31. 31.

    Wang S, Szalay MS, Zhang C, Csermely P. Learning and innovative elements of strategy adoption rules expand cooperative network topologies. PloS one. 2008;3(4):e1917 Epub 2008/04/10. PubMed Central PMCID: PMC2275790.

    Not in our library10.1371/journal.pone.0001917

32. 32.

    Newman ME. Modularity and community structure in networks. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(23):8577–82. Epub 2006/05/26. PubMed Central PMCID: PMC1482622.

    Not in our library10.1073/pnas.0601602103

33. 33.

    Sporns O. Network attributes for segregation and integration in the human brain. Current opinion in neurobiology. 2013;23(2):162–71. Epub 2013/01/09.

    Not in our library10.1016/j.conb.2012.11.015

34. 34.

    Li Z, Li Y, Yi Y, Huang W, Yang S, Niu W, et al Dissecting a central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation. Nature communications. 2012;3:776 Epub 2012/04/12.

    Not in our library10.1038/ncomms1780

35. 35.

    Chase DL, Pepper JS, Koelle MR. Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans. Nature neuroscience. 2004;7(10):1096–103. Epub 2004/09/21.

    Not in our library10.1038/nn1316

36. 36.

    van den Heuvel MP, Sporns O. Rich-club organization of the human connectome. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2011;31(44):15775–86. Epub 2011/11/04.

    Not in our library10.1523/jneurosci.3539-11.2011

37. 37.
    Rich Club Organization of Macaque Cerebral Cortex and Its Role in Network Communication · 2012

    No notice
38. 38.

    de Reus MA, van den Heuvel MP. Rich club organization and intermodule communication in the cat connectome. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2013;33(32):12929–39. Epub 2013/08/09.

    Not in our library10.1523/jneurosci.1448-13.2013

39. 39.

    Shih CT, Sporns O, Yuan SL, Su TS, Lin YJ, Chuang CC, et al Connectomics-based analysis of information flow in the Drosophila brain. Current biology: CB. 2015;25(10):1249–58. Epub 2015/04/14.

    Not in our library10.1016/j.cub.2015.03.021

40. 40.

    Colizza V, Flammini A, Serrano MA, Vespignani A. Detecting rich-club ordering in complex networks. Nature Physics. 2006;2(2):110–5.

    Not in our library

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