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Chemosensory organs as models of neuronal synapses

Abstract

Neuronal synapses are important microstructures that underlie complex cognitive capacities. Recent studies, primarily in Caenorhabditis elegans and Drosophila melanogaster, have revealed surprising parallels between these synapses and the 'chemosensory synapses' that reside at the tips of chemosensory cells that respond to environmental stimuli. Similarities in the structures, mechanisms of action and specific molecules found at these sites extend to the presynaptic, postsynaptic and glial entities composing both synapse types. In this article I propose that chemosensory synapses may serve as useful models of neuronal synapses, and consider the possibility that the two synapse types derive from a common ancestral structure.

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Figure 1: Similarities between sensory receptive endings and neuron–neuron synapses.
Figure 2: Neurotransmitter receptor-related proteins are expressed at sensory receptive endings.
Figure 3: C. elegans CEPsh glia envelop sensory and neuron–neuron synapses.

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References

  1. Kandel, E. R. & Siegelbaum, S. A. in Principles of Neural Science (eds Kandel, E. R., Schwartz, J. H. & Jessell, T. M.) 175–186 (McGraw-Hill, 2000).

    Google Scholar 

  2. Spacek, J. Three-dimensional analysis of dendritic spines. III. Glial sheath. Anat. Embryol. (Berl.) 171, 245–252 (1985).

    Article  CAS  Google Scholar 

  3. Ventura, R. & Harris, K. M. Three-dimensional relationships between hippocampal synapses and astrocytes. J. Neurosci. 19, 6897–6906 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Shaham, S. Glia-neuron interactions in nervous system function and development. Curr. Top. Dev. Biol. 69, 39–66 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Benton, R., Vannice, K. S., Gomez-Diaz, C. & Vosshall, L. B. Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila. Cell 136, 149–162 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mayer, M. L. & Armstrong, N. Structure and function of glutamate receptor ion channels. Annu. Rev. Physiol. 66, 161–181 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. Mayer, M. L. Glutamate receptors at atomic resolution. Nature 440, 456–462 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Bargmann, C. I. & Horvitz, H. R. Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans. Neuron 7, 729–742 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. Nelson, G. et al. An amino-acid taste receptor. Nature 416, 199–202 (2002).

    Article  CAS  PubMed  Google Scholar 

  10. Alioto, T. S. & Ngai, J. The repertoire of olfactory C family G protein-coupled receptors in zebrafish: candidate chemosensory receptors for amino acids. BMC Genomics 7, 309 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Chandrashekar, J., Hoon, M. A., Ryba, N. J. & Zuker, C. S. The receptors and cells for mammalian taste. Nature 444, 288–294 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Schwartz, J. H. in Principles of Neural Science (eds Kandel, E. R., Schwartz, J. H. & Jessell, T. M.) 280–297 (McGraw-Hill, 2000).

    Google Scholar 

  13. Yassin, L. et al. Characterization of the deg-3/des-2 receptor: a nicotinic acetylcholine receptor that mutates to cause neuronal degeneration. Mol. Cell. Neurosci. 17, 589–599 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Alberts, B. et al. in Molecular Biology of the Cell 5th edn (eds Alberts, B. et al.) 619–620 (Garland Science, 2008).

    Google Scholar 

  15. Sambongi, Y. et al. Caenorhabditis elegans senses protons through amphid chemosensory neurons: proton signals elicit avoidance behavior. Neuroreport 11, 2229–2232 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Beg, A. A., Ernstrom, G. G., Nix, P., Davis, M. W. & Jorgensen, E. M. Protons act as a transmitter for muscle contraction in C. elegans. Cell 132, 149–160 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Crump, J. G., Zhen, M., Jin, Y. & Bargmann, C. I. The SAD-1 kinase regulates presynaptic vesicle clustering and axon termination. Neuron 29, 115–129 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Hung., W., Hwang, C., Po, M. D. & Zhen, M. Neuronal polarity is regulated by a direct interaction between a scaffolding protein, Neurabin, and a presynaptic SAD-1 kinase in Caenorhabditis elegans. Development 134, 237–249 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Dwyer, N. D., Adler, C. E., Crump, J. G., L'Etoile, N. D. & Bargmann, C. I. Polarized dendritic transport and the AP-1 mu1 clathrin adaptor UNC-101 localize odorant receptors to olfactory cilia. Neuron 31, 277–287 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Margeta, M. A., Wang, G. J. & Shen, K. Clathrin adaptor AP-1 complex excludes multiple postsynaptic receptors from axons in C. elegans. Proc. Natl Acad. Sci. USA 106, 1632–1637 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Satoh, A. K., O'Tousa, J. E., Ozaki, K. & Ready, D. F. Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors. Development 132, 1487–1497 (2005).

    Article  CAS  PubMed  Google Scholar 

  22. Brown, T. C., Correia, S. S., Petrok, C. N. & Esteban, J. A. Functional compartmentalization of endosomal trafficking for the synaptic delivery of AMPA receptors during long-term potentiation. J. Neurosci. 27, 13311–13315 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rosenbaum, J. L. & Carlson, K. Cilia regeneration in Tetrahymena and its inhibition by colchicine. J. Cell Biol. 40, 415–425 (1969).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Matus, A., Ackermann, M., Pehling, G., Byers, H. R. & Fujiwara, K. High actin concentrations in brain dendritic spines and postsynaptic densities. Proc. Natl Acad. Sci. USA 79, 7590–7594 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sekerkova, G., Zheng, L., Loomis, P. A., Mugnaini, E. & Bartles, J. R. Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli. Cell. Mol. Life Sci. 63, 2329–2341 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sekerkova, G. et al. Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells. J. Neurosci. 24, 5445–5456 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Flock, A. & Duvall, A. J. The ultrastructure of the kinocilium of the sensory cells in the inner ear and lateral line organs. J. Cell Biol. 25, 1–8 (1965).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Flock, A. & Cheung, H. C. Actin filaments in sensory hairs of inner ear receptor cells. J. Cell Biol. 75, 339–343 (1977).

    Article  CAS  PubMed  Google Scholar 

  29. Perkins, L. A., Hedgecock, E. M., Thomson, J. N. & Culotti, J. G. Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev. Biol. 117, 456–487 (1986).

    Article  CAS  PubMed  Google Scholar 

  30. Ward, S., Thomson, N., White, J. G. & Brenner, S. Electron microscopical reconstruction of the anterior sensory anatomy of the nematode Caenorhabditis elegans. J. Comp. Neurol. 160, 313–337 (1975).

    Article  CAS  PubMed  Google Scholar 

  31. Satterlee, J. S. et al. Specification of thermosensory neuron fate in C. elegans requires ttx-1, a homolog of otd/Otx. Neuron 31, 943–956 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Bacaj, T., Tevlin, M., Lu, Y. & Shaham, S. Glia are essential for sensory organ function in C. elegans. Science 322, 744–747 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jaworski, J. et al. Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity. Neuron 61, 85–100 (2009).

    Article  CAS  PubMed  Google Scholar 

  34. Nimchinsky, E. A., Sabatini, B. L. & Svoboda, K. Structure and function of dendritic spines. Annu. Rev. Physiol. 64, 313–353 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Yasumatsu, N., Matsuzaki, M., Miyazaki, T., Noguchi, J. & Kasai, H. Principles of long-term dynamics of dendritic spines. J. Neurosci. 28, 13592–13608 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. McEwen, B. S. & Milner, T. A. Hippocampal formation: shedding light on the influence of sex and stress on the brain. Brain Res. Rev. 55, 343–355 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Li, C. et al. Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice. Proc. Natl Acad. Sci. USA 101, 2185–2190 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mukhopadhyay, S., Lu, Y., Shaham, S. & Sengupta, P. Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans. Dev. Cell 14, 762–774 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Albert, P. S. & Riddle, D. L. Developmental alterations in sensory neuroanatomy of the Caenorhabditis elegans dauer larva. J. Comp. Neurol. 219, 461–481 (1983).

    Article  CAS  PubMed  Google Scholar 

  40. Swoboda, P., Adler, H. T. & Thomas, J. H. The RFX-type transcription factor DAF-19 regulates sensory neuron cilium formation in C. elegans. Mol. Cell 5, 411–421 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Senti, G. & Swoboda, P. Distinct isoforms of the RFX transcription factor DAF-19 regulate ciliogenesis and maintenance of synaptic activity. Mol. Biol. Cell 19, 5517–5528 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Siegelbaum, S. A., Schwartz, J. H. & Kandel, E. R. in Principles of Neural Science (eds Kandel, E. R., Schwartz, J. H. & Jessell, T. M.) 229–252 (McGraw-Hill, 2000).

    Google Scholar 

  43. Buck, L. & Axel, R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65, 175–187 (1991).

    Article  CAS  PubMed  Google Scholar 

  44. Troemel, E. R., Chou, J. H., Dwyer, N. D., Colbert, H. A. & Bargmann, C. I. Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans. Cell 83, 207–218 (1995).

    Article  CAS  PubMed  Google Scholar 

  45. Palczewski, K. et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289, 739–745 (2000).

    Article  CAS  PubMed  Google Scholar 

  46. Kim, E. & Sheng, M. PDZ domain proteins of synapses. Nature Rev. Neurosci. 5, 771–781 (2004).

    Article  CAS  Google Scholar 

  47. Tsunoda, S. et al. A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade. Nature 388, 243–249 (1997).

    Article  CAS  PubMed  Google Scholar 

  48. Li, Z., Benard, O. & Margolskee, R. F. Ggamma13 interacts with PDZ domain-containing proteins. J. Biol. Chem. 281, 11066–11073 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Heiman, M. G. & Shaham, S. Ancestral roles of glia suggested by the nervous system of Caenorhabditis elegans. Neuron Glia Biol. 3, 55–61 (2007).

    Article  PubMed  Google Scholar 

  50. Peters, A., Palay, S. L. & Webster, H. D. in The Fine Structure of the Nervous System 273–311 (Oxford Univ. Press, 1991).

    Google Scholar 

  51. Todd, K. J. & Robitaille, R. Neuron-glia interactions at the neuromuscular synapse. Novartis Found. Symp. 276, 222–229; discussion 229–237, 275–281 (2006).

    CAS  PubMed  Google Scholar 

  52. Finnemann, S. C. Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors. EMBO J. 22, 4143–4154 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Suzuki, Y., Takeda, M. & Farbman, A. I. Supporting cells as phagocytes in the olfactory epithelium after bulbectomy. J. Comp. Neurol. 376, 509–517 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. Hansel, D. E., Eipper, B. A. & Ronnett, G. V. Neuropeptide Y functions as a neuroproliferative factor. Nature 410, 940–944 (2001).

    Article  CAS  PubMed  Google Scholar 

  55. Nenov, A. P., Chen, C. & Bobbin, R. P. Outward rectifying potassium currents are the dominant voltage activated currents present in Deiters' cells. Hear. Res. 123, 168–182 (1998).

    Article  CAS  PubMed  Google Scholar 

  56. Rio, C., Dikkes, P., Liberman, M. C. & Corfas, G. Glial fibrillary acidic protein expression and promoter activity in the inner ear of developing and adult mice. J. Comp. Neurol. 442, 156–162 (2002).

    Article  CAS  PubMed  Google Scholar 

  57. Brechbuhl, J., Klaey, M. & Broillet, M. C. Grueneberg ganglion cells mediate alarm pheromone detection in mice. Science 321, 1092–1095 (2008).

    Article  PubMed  CAS  Google Scholar 

  58. Mamasuew, K., Breer, H. & Fleischer, J. Grueneberg ganglion neurons respond to cool ambient temperatures. Eur. J. Neurosci. 28, 1775–1785 (2008).

    Article  PubMed  Google Scholar 

  59. Smit, A. B. et al. A glia-derived acetylcholine-binding protein that modulates synaptic transmission. Nature 411, 261–268 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Suh, J. & Jackson, F. R. Drosophila ebony activity is required in glia for the circadian regulation of locomotor activity. Neuron 55, 435–447 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Christopherson, K. S. et al. Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120, 421–433 (2005).

    Article  CAS  PubMed  Google Scholar 

  62. Yoshimura, S., Murray, J. I., Lu, Y., Waterston, R. H. & Shaham, S. mls-2 and vab-3 control glia development, hlh-17/Olig expression and glia-dependent neurite extension in C. elegans. Development 135, 2263–2275 (2008).

    Article  CAS  PubMed  Google Scholar 

  63. White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos. Trans. R. Soc. Lond. B Biol. Sci. 314, 1–340 (1986).

    Article  CAS  PubMed  Google Scholar 

  64. Westfall, J. A., Wilson, J. D., Rogers, R. A. & Kinnamon, J. C. Multifunctional features of a gastrodermal sensory cell in hydra: three-dimensional study. J. Neurocytol. 20, 251–261 (1991).

    Article  CAS  PubMed  Google Scholar 

  65. Sakarya, O. et al. A post-synaptic scaffold at the origin of the animal kingdom. PLoS ONE 2, e506 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Leys, S. P. & Degnan, B. M. Cytological basis of photoresponsive behavior in a sponge larva. Biol. Bull. 201, 323–338 (2001).

    Article  CAS  PubMed  Google Scholar 

  67. Shah, A. S., Ben-Shahar, Y., Moninger, T. O., Kline, J. N. & Welsh, M. J. Motile cilia of human airway epithelia are chemosensory. Science 325, 1131–1134 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. L'Etoile, N. D. et al. The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory adaptation in C. elegans. Neuron 36, 1079–1089 (2002).

    Article  CAS  PubMed  Google Scholar 

  69. Kaye, J. A., Rose, N. C., Goldsworthy, B., Goga, A. & L'Etoile, N. D. A 3'UTR pumilio-binding element directs translational activation in olfactory sensory neurons. Neuron 61, 57–70 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. O'Halloran, D. M., Altshuler-Keylin, S., Lee, J. I. & L'Etoile, N. D. Regulators of AWC mediated olfactory plasticity in Caenorhabditis elegans. PLoS Genet. (in the press).

  71. Bliss, T. V. & Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 232, 331–356 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Slack, J. R. & Pockett, S. Cyclic AMP induces long-term increase in synaptic efficacy in CA1 region of rat hippocampus. Neurosci. Lett. 130, 69–72 (1991).

    Article  CAS  PubMed  Google Scholar 

  73. Thompson, K. R. et al. Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway. Neuron 44, 997–1009 (2004).

    CAS  PubMed  Google Scholar 

  74. Mauch, D. H. et al. CNS synaptogenesis promoted by glia-derived cholesterol. Science 294, 1354–1357 (2001).

    Article  CAS  PubMed  Google Scholar 

  75. Fuentes-Medel, Y. et al. Glia and muscle sculpt neuromuscular arbors by engulfing destabilized synaptic boutons and shed presynaptic debris. PLoS Biol. 7, e1000184 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Colon-Ramos, D. A., Margeta, M. A. & Shen, K. Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans. Science 318, 103–106 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Murai, K. K., Nguyen, L. N., Irie, F., Yamaguchi, Y. & Pasquale, E. B. Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling. Nature Neurosci. 6, 153–160 (2003).

    Article  CAS  PubMed  Google Scholar 

  78. Rothstein, J. D. et al. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16, 675–686 (1996).

    Article  CAS  PubMed  Google Scholar 

  79. Adams, R. H. et al. Gene structure and glial expression of the glycine transporter GlyT1 in embryonic and adult rodents. J. Neurosci. 15, 2524–2532 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Minelli, A., DeBiasi, S., Brecha, N. C., Zuccarello, L. V. & Conti, F. GAT-3, a high-affinity GABA plasma membrane transporter, is localized to astrocytic processes, and it is not confined to the vicinity of GABAergic synapses in the cerebral cortex. J. Neurosci. 16, 6255–6264 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Araque, A., Parpura, V., Sanzgiri, R. P. & Haydon, P. G. Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur. J. Neurosci. 10, 2129–2142 (1998).

    Article  CAS  PubMed  Google Scholar 

  82. Heumann, R., Villegas, J. & Herzfeld, D. W. Acetylcholine synthesis in the Schwann cell and axon in the giant nerve fiber of the squid. J. Neurochem. 36, 765–768 (1981).

    Article  CAS  PubMed  Google Scholar 

  83. Minchin, M. C. & Iversen, L. L. Release of (3H)gamma-aminobutyric acid from glial cells in rat dorsal root ganglia. J. Neurochem. 23, 533–540 (1974).

    Article  CAS  PubMed  Google Scholar 

  84. Newman, E. A. Glial cell inhibition of neurons by release of ATP. J. Neurosci. 23, 1659–1666 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Oliet, S. H. & Mothet, J. P. Regulation of N-methyl-D-aspartate receptors by astrocytic D-serine. Neuroscience 158, 275–283 (2009).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

I would like to thank J. Darnell, M. Heiman, M. Nedergaard and L. Vosshall for comments and discussions of the ideas presented here and R. Benton and Y. Lu for sharing images. This work was supported in part by US National Institutes of Health grant R01NS064273.

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Shaham, S. Chemosensory organs as models of neuronal synapses. Nat Rev Neurosci 11, 212–217 (2010). https://doi.org/10.1038/nrn2740

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