Abstract
To establish the relationship between locomotory behavior and dynamics of neural circuits in the nematode C. elegans we combined molecular and theoretical approaches. In particular, we quantitatively analyzed the motion of C. elegans with defective synaptic GABA and acetylcholine transmission, defective muscle calcium signaling, and defective muscles and cuticle structures, and compared the data with our systems level circuit model. The major experimental findings are: (1) anterior-to-posterior gradients of body bending flex for almost all strains both for forward and backward motion, and for neuronal mutants, also analogous weak gradients of undulatory frequency, (2) existence of some form of neuromuscular (stretch receptor) feedback, (3) invariance of neuromuscular wavelength, (4) biphasic dependence of frequency on synaptic signaling, and (5) decrease of frequency with increase of the muscle time constant. Based on (1) we hypothesize that the Central Pattern Generator (CPG) is located in the head both for forward and backward motion. Points (1) and (2) are the starting assumptions for our theoretical model, whose dynamical patterns are qualitatively insensitive to the details of the CPG design if stretch receptor feedback is sufficiently strong and slow. The model reveals that stretch receptor coupling in the body wall is critical for generation of the neuromuscular wave. Our model agrees with our behavioral data (3), (4), and (5), and with other pertinent published data, e.g., that frequency is an increasing function of muscle gap-junction coupling.
Similar content being viewed by others
References
Akay, T., Haehn, S., Schmitz, J., & Buschges, A. (2004). Signals from load sensors underlie interjoint coordination during stepping movements of the stick insect leg. Journal of Neurophysiology, 92, 42–51.
Bargmann, C. I. (1998). Neurobiology of the Caenorhabditis elegans genome. Science, 282, 2028–2033.
Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics, 77, 71–94.
Bryden, J., & Cohen, N. (2004). A simulation model of the locomotion controlers for the nematode Caenorhabditis elegans. In: S. Schaal et al. (Eds.), From animals to animats 8: Proc. Eight Intern. Conf. on Simulation of Adaptive Behavior (pp. 183–192). Cambridge: MIT Press.
Chalfie, M., & White, J. (1988). The nervous system. In: W. B. Wood (Ed.), The nematode Caenorhabditis elegans (pp. 337–391). Cold Spring Harbor: Cold Spring Harbor Laboratory Press.
Chalfie, M., et al. (1985). The neural circuit for touch sensitivity in Caenorhabditis elegans. Journal of Neuroscience, 5, 956–964.
Chen, B. L., Hall, D. H., & Chklovskii, D. B. (2006). Wiring optimization can relate neuronal structure and function. Proceedings of the National Academy of Sciences of the United States of America, 103, 4723–4728.
Cronin, C. J., et al. (2005). An automated system for measuring parameters of nematode sinusoidal movement. BMC Genetics, 6, 5.
Davis, R. E., & Stretton, A. O. W. (1989). Signaling properties of Ascaris motorneurons: Graded active responses, graded synaptic transmission and tonic transmitter release. Journal of Neuroscience, 9, 415–425.
Davies, A. G., et al. (2003). A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans. Cell, 115, 655–666.
Delcomyn, F. (1980). Neural basis of rhythmic behavior in animals. Science, 210, 492–498.
de Bono, M., & Maricq, A. V. (2005). Neuronal substrates of complex behaviors in C. elegans. Annual Review of Neuroscience, 28, 451–501.
Francis, M. M., Mellem, J. E., & Maricq, A. V. (2003). Bridging the gap between genes and behavior: recent advances in the electrophysiological analysis of neural function in Caenorhabditis elegans. Trends in Neurosciences, 26, 90–99.
Friesen, W. O., & Cang, J. (2001). Sensory and central mechanisms control intersegmental coordination. Current Opinion in Neurobiology, 11, 678–683.
Gengyo-Ando, K., et al. (1993). The C. elegans unc-18 gene encodes a protein expressed in motor neurons. Neuron, 11, 703–711.
Goodman, M. B., Hall, D. H., Avery, L., & Lockery, S. R. (1998). Active currents regulate sensitivity and dynamic range in C. elegans neurons. Neuron, 20, 763–772.
Goodman, M. B., & Schwarz, E. M. (2003). Transducing touch in Caenorhabditis elegans. Annual Review of Physiology, 65, 429–452.
Gray, J. M., Hill, J. J., & Bargmann, C. I. (2005). A circuit for navigation in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 102, 3184–3191.
Grillner, S. (1975). Locomotion in vertebrates: Central mechanisms and reflex interaction. Physiological Reviews, 55, 247–303.
Hobert, O. (2003). Behavioral plasticity in C. elegans: Paradigms, circuits, genes. Journal of Neurobiology, 54, 203–223.
Jin, Y., et al. (1999). The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase and is required for synaptic transmission but not synaptic development. Journal of Neuroscience, 19, 539–548.
Jospin, M., Jacquemond, V., Mariol, M. C., Segalat, L., & Allard, B. (2002). The L-type voltage-dependent Ca2 + channel EGL-19 controls body wall muscle function in Caenorhabditis elegans. Journal of Cell Biology, 159, 337–347.
Karbowski, J., Cronin, C. J., Seah, A., Mendel, J. E., Cleary, D., & Sternberg, P. W. (2006). Conservation rules, their breakdown, and optimality in Caenorhabditis sinusoidal locomotion. Journal of Theoretical Biology, 242, 652–669.
Lee, R. Y. N., Lobel, L., Hengartner, M., Horvitz, H. R., & Avery, L. (1997). Mutations in the α1 subunit of an L-type voltage-activated Ca2 + channel cause myotonia in Caenorhabditis elegans. EMBO Journal, 16, 6066–6076.
Li, W., Feng, Z., Sternberg, P. W., & Xu, X. Z. S. (2006). A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue. Nature, 440, 684–687.
Liu, Q., Chen, B., Gaier, E., Joshi, J., & Wang, Z.-W. (2006). Low conductance gap junctions mediate specific electrical coupling in body-wall muscle cells of Caenorhabdidtis elegans. Journal of Biological Chemistry, 281, 7881–7889.
Maduro, M., & Pilgrim, D. (1995). Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system. Genetics, 141, 977–988.
Marder, E., & Calabrese, R. L. (1996). Principles of rhythmic motor pattern generation. Physiological Reviews, 76, 687–717.
Marder, E., Bucher, D., Schulz, D. J., & Taylor, A. L. (2005). Invertebrate central pattern generation moves along. Current Biology, 15, R685–R699.
Maryon, E. B., Coronado, R., & Anderson, P. (1996). unc-68 encodes a ryanodine receptor involved in regulating C. elegans body-wall muscle contraction. Journal of Cell Biology, 134, 885–893.
Maryon, E. B., Saari, B., & Anderson, P. (1998). Muscle-specific functions of ryanodine receptor channels in Caenorhabditis elegans. Journal of Cell Science, 111, 2885–2895.
McIntire, S. L., Jorgensen, E., Kaplan, J., & Horvitz, H. R. (1993). The GABAergic nervous system of Caenorhabditis elegans. Nature, 364, 337–341.
Mendel, J. E., et al. (1995). Participation of the protein Go in multiple aspects of behavior in C. elegans. Science, 267, 1652–1655.
Moerman, D. G., & Fire, A. (1997). Muscle: Structure, function, and development. In D. L. Riddle, et al. (Eds.), C. elegans II (pp. 417–470). Cold Spring Harbor: Cold Spring Harbor Laboratory Press.
Niebur, E., & Erdos, P. (1991). Theory of the locomotion of nematodes. Biophysical Journal, 60, 1132–1146.
Nusbaum, M. P., & Beenhakker M. P. (2002). A small-systems approach to motor pattern generation. Nature, 417, 343–350.
Okuda, T., Haga, T., Kanai, Y., Endou, H., Ishihara, T., & Katsura, I. (2000). Identification and characterization of the high-affinity choline transporter. Nature Neuroscience, 3, 120–125.
Schuske, K., Beg, A. A., & Jorgensen, E. M. (2004). The GABA nervous system in C. elegans. Trends in Neurosciences, 27, 407–414.
Segalat, L., Elkes, D. A., & Kaplan, J. M. (1995). Modulation of serotonin-controlled behaviors by Go in Caenorhabditis elegans. Science, 267, 1648–1651.
Skinner, F. K., & Mulloney, B. (1998). Intersegmental coordination in invertebrates and vertebrates. Current Opinion in Neurobiology, 8, 725–732.
Strogatz, S. H. (1994). Nonlinear dynamics and chaos. Westview Press.
Suzuki, H., et al. (2003). In vivo imaging of C. elegans mechanosensory neurons demonstrates a specific role for the MEC-4 channel in the process of gentle touch sensation. Neuron, 39, 1005–1017.
Tavernarakis, N., Shreffler, W., Wang, S., & Driscoll, M. (1997). unc-8, a DEG/ENaC family member, encodes a subunit of a candidate mechanically gated channel that modulates C. elegans locomotion. Neuron, 18, 107–119.
Wang, Z. W., Saifee, O., Nonet, M. L., & Salkoff, L. (2001). Slo-1 potassium channels control quantal content of neurotransmitter release at the C. elegans neuromuscular junction. Neuron, 32, 867–881.
Weimer, R. M., et al. (2003). Defects in synaptic vesicle docking in unc-18 mutants. Nature Neuroscience, 6, 1023–1030.
White, J. G., Southgate, E., Thomson, J. N., & Brenner, S. (1986). The structure of the nervous system of the nematode Caenorhabditis elegans. Philosophical Transactions of the Royal Society of London. B, 314, 1–340.
Wicks, S. R., Roehrig, C. J., & Rankin, C. H. (1996). A dynamic network simulation of the nematode tap withdrawal circuits: Predictions concerning synaptic function using behavioral criteria. Journal of Neuroscience, 16, 4017–4031.
Author information
Authors and Affiliations
Corresponding author
Additional information
Action Editor: Frances K. Skinner
Electronic supplementary material
Below is the link to the supplementary materials
Rights and permissions
About this article
Cite this article
Karbowski, J., Schindelman, G., Cronin, C.J. et al. Systems level circuit model of C. elegans undulatory locomotion: mathematical modeling and molecular genetics. J Comput Neurosci 24, 253–276 (2008). https://doi.org/10.1007/s10827-007-0054-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10827-007-0054-6